1,3-Diamino-2-hydroxypropane pro-drug derivatives

ABSTRACT

The present invention relates to compounds of formula (AA) (I) and (X):  
                 
 
     useful in treating Alzheimer&#39;s disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer&#39;s disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from U.S. ProvisionalApplication Serial No. 60/408,783, filed Sep. 6, 2002, which isincorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The invention relates to 1,3-diamino-2-hydroxypropane prodrugderivatives and to such compounds that are useful in the treatment ofAlzheimer's disease and related diseases. More specifically, it relatesto such compounds that are capable of yielding or generating, either invitro or in vivo, compounds that inhibit beta-secretase, an enzyme thatcleaves amyloid precursor protein to produce amyloid beta peptide (Abeta), a major component of the amyloid plaques found in the brains ofAlzheimer's sufferers.

[0004] 2. Background of the Invention

[0005] Alzheimer's disease (AD) is a progressive degenerative disease ofthe brain primarily associated with aging. Clinical presentation of ADis characterized by loss of memory, cognition, reasoning, judgment, andorientation. As the disease progresses, motor, sensory, and linguisticabilities are also affected until there is global impairment of multiplecognitive functions. These cognitive losses occur gradually, buttypically lead to severe impairment and eventual death in the range offour to twelve years.

[0006] Alzheimer's disease is characterized by two major pathologicobservations in the brain: neurofibrillary tangles and beta amyloid (orneuritic) plaques, comprised predominantly of an aggregate of a peptidefragment know as A beta. Individuals with AD exhibit characteristicbeta-amyloid deposits in the brain (beta amyloid plaques) and incerebral blood vessels (beta amyloid angiopathy) as well asneurofibrillary tangles. Neurofibrillary tangles occur not only inAlzheimer's disease but also in other dementia-inducing disorders. Onautopsy, large numbers of these lesions are generally found in areas ofthe human brain important for memory and cognition.

[0007] Smaller numbers of these lesions in a more restricted anatomicaldistribution are found in the brains of most aged humans who do not haveclinical AD. Amyloidogenic plaques and vascular amyloid angiopathy alsocharacterize the brains of individuals with Trisomy 21 (Down'sSyndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of theDutch-Type (HCHWA-D), and other neurodegenerative disorders.Beta-amyloid is a defining feature of AD, now believed to be a causativeprecursor or factor in the development of disease. Deposition of A betain areas of the brain responsible for cognitive activities is a majorfactor in the development of AD. Beta-amyloid plaques are predominantlycomposed of amyloid beta peptide (A beta, also sometimes designatedbetaA4). A beta peptide is derived by proteolysis of the amyloidprecursor protein (APP) and is comprised of 39-42 amino acids. Severalproteases called secretases are involved in the processing of APP.

[0008] Cleavage of APP at the N-terminus of the A beta peptide bybeta-secretase and at the C-terminus by one or more gamma-secretasesconstitutes the beta-amyloidogenic pathway, i.e. the pathway by which Abeta is formed. Cleavage of APP by alpha-secretase produces alpha-sAPP,a secreted form of APP that does not result in beta-amyloid plaqueformation. This alternate pathway precludes the formation of A betapeptide. A description of the proteolytic processing fragments of APP isfound, for example, in U.S. Pat. Nos. 5,441,870; 5,721,130; and5,942,400.

[0009] An aspartyl protease has been identified as the enzymeresponsible for processing of APP at the beta-secretase cleavage site.The beta-secretase enzyme has been disclosed using varied nomenclature,including BACE, Asp, and Memapsin. See, for example, Sinha et al., 1999,Nature 402:537-554 (p501) and published PCT application WO00/17369.

[0010] Several lines of evidence indicate that progressive cerebraldeposition of beta-amyloid peptide (A beta) plays a seminal role in thepathogenesis of AD and can precede cognitive symptoms by years ordecades. See, for example, Selkoe, 1991, Neuron 6:487. Release of A betafrom neuronal cells grown in culture and the presence of A beta incerebrospinal fluid (CSF) of both normal individuals and AD patients hasbeen demonstrated. See, for example, Seubert et al., 1992, Nature359:325-327.

[0011] It has been proposed that A beta peptide accumulates as a resultof APP processing by beta-secretase, thus inhibition of this enzyme'sactivity is desirable for the treatment of AD. In vivo processing of APPat the beta-secretase cleavage site is thought to be a rate-limitingstep in A beta production, and is thus a therapeutic target for thetreatment of AD. See for example, Sabbagh, M., et al., 1997, Alz. Dis.Rev. 3, 1-19.

[0012] BACE1 knockout mice fail to produce A beta, and present a normalphenotype. When crossed with transgenic mice that over express APP, theprogeny show reduced amounts of A beta in brain extracts as comparedwith control animals (Luo et al., 2001 Nature Neuroscience 4:231-232).This evidence further supports the proposal that inhibition ofbeta-secretase activity and reduction of A beta in the brain provides atherapeutic method for the treatment of AD and other beta amyloiddisorders.

[0013] At present there are no effective treatments for halting,preventing, or reversing the progression of Alzheimer's disease.Therefore, there is an urgent need for pharmaceutical agents capable ofslowing the progression of Alzheimer's disease and/or preventing it inthe first place.

[0014] Compounds that are effective inhibitors of beta-secretase, thatinhibit beta-secretase-mediated cleavage of APP, that are effectiveinhibitors of A beta production, and/or are effective to reduce amyloidbeta deposits or plaques, are needed for the treatment and prevention ofdisease characterized by amyloid beta deposits or plaques, such as AD.

SUMMARY OF THE INVENTION

[0015] The invention encompasses the compounds of formula (AA), (I) and(X) shown below, pharmaceutical compositions containing the compoundsand methods employing such compounds or compositions in the treatment ofAlzheimer's disease and more specifically compounds that are capable ofinhibiting beta-secretase, an enzyme that cleaves amyloid precursorprotein to produce A-beta peptide, a major component of the amyloidplaques found in the brains of Alzheimer's sufferers.

[0016] In one aspect, the invention provides compounds of the formulaAA:

[0017] and pharmaceutically acceptable salts thereof, wherein one ofR_(N) and R_(N)′ is hydrogen and

[0018] the other is —C(═O)—(CRR′)₀₋₆R₁₀₀, —C(═O)—(CRR′)₁₋₆—O—R′₁₀₀,—C(═O)—(CRR′)₁₋₆—S—R′₁₀₀, —C(═O)—(CRR′)₁₋₆—C(═O)—R₁₀₀,—C(═O)—(CRR′)₁₋₆—SO₂—R₁₀₀, —C(═O)—(CRR′)₁₋₆—NR₁₀₀—R′₁₀₀, or

[0019] wherein

[0020] R₄ is selected from the group consisting of H; NH₂;—NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; C₁-C₄ alkyl-NHC(O)R₅;—(CH₂)₀₋₄R₈; —O—C₁-C₄ alkanoyl; OH; C₆-C₁₀ aryloxy optionallysubstituted with 1, 2, or 3 groups that are independently halogen, C₁-C₄alkyl, —CO₂H, —C(O)—C₁-C₄ alkoxy, or C₁-C₄ alkoxy; C₁-C₆ alkoxy; arylC₁-C₄ alkoxy; —NR₅₀CO₂R₅₁; —C₁-C₄ alkyl-NR₅₀CO₂R₅; —C≡N; —CF₃; —CF₂—CF₃;—C≡CH; —CH₂—CH═CH₂; —(CH₂)₁₋₄—R₄₋₁; —(CH₂)₁₋₄—NH—R₄₋₁;—O—(CH₂)_(n6)—R₄₋₁; —S—(CH₂)_(n6)—R₄₋₁; —(CH₂)₀₋₄—NHC(O)—(CH₂)₀₋₆—R₅₂;—(CH₂)₀₋₄—R₅₃—(CH₂)₀₋₄—R₅₄;

[0021] wherein

[0022] n₆ is 0, 1, 2, or 3;

[0023] n₇ is 0, 1, 2, or 3;

[0024] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0025] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0026] R₄₋₄ is alkyl, arylalkyl, alkanoyl, or arylalkanoyl;

[0027] R₄₋₆ is —H or C₁-C₆ alkyl;

[0028] R₅ is selected from the group consisting of C₃-C₇ cycloalkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆ heterocycloalkyl,C₅-C₆ heteroaryl, C₆-C₁₀ aryl, C₃-C₇ cycloalkyl C₁-C₄ alkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, C₆-C₁₀aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that areindependently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0029] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, phenyl C₁-C₄alkyl;

[0030] R₈ is selected from the group consisting of —SO₂-heteroaryl,—SO₂-aryl, —SO₂-heterocycloalkyl, —SO₂—C₁-C₁₀ alkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₁-C₆ alkyl, —S—C₂-C₄ alkanoyl, wherein

[0031] R₉ is aryl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl;

[0032] R₅₁ is selected from the group consisting of aryl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, heteroaryl, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇cycloalkyl, or —C₁-C₄ alkoxy; heterocycloalkyl optionally substitutedwith 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, C₂-C₄ alkanoyl, aryl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl;alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3groups that are independently OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); heteroarylalkyloptionally substituted with 1, 2, or 3 groups that are independentlyC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆alkyl)(C₁-C₆ alkyl); aryl; heterocycloalkyl; C₃-C₈ cycloalkyl; andcycloalkylalkyl; wherein the aryl; heterocycloalkyl, C₃-C₈ cycloalkyl,and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or5 groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy;

[0033] R₅₂ is heterocycloalkyl, heteroaryl, aryl, cycloalkyl,—S(O)₀₋₂—C₁-C₆ alkyl, CO₂H, —C(O)NH₂, —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —CO₂-alkyl, —NHS(O)₀₋₂—C₁-C₆ alkyl, —N(alkyl)S(O)₀₋₂—C₁-C₆alkyl, —S(O)₀₋₂-heteroaryl, —S(O)₀₋₂-aryl, —NH(arylalkyl),—N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionallysubstituted with 1, 2, 3, 4, or 5 groups that are independently alkyl,alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO₂, CN,alkoxycarbonyl, or aminocarbonyl;

[0034] R₅₃ is absent, —O—, —C(O)—, —NH—, —N(alkyl)-, —NH—S(O)₀₋₂—,—N(alkyl)-S(O)₀₋₂—, —S(O)₀₋₂—NH—, —S(O)₀₋₂—N(alkyl)-, —NH—C(S)—, or—N(alkyl)-C(S)—;

[0035] R₅₄ is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO₂H,—CO₂-alkyl, —C(O)NH(alkyl), —C(O)N(alkyl) (alkyl), —C(O)NH₂, C₁-C₈alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH₂, NH(alkyl), N(alkyl)(alkyl), or —C₁-C₆ alkyl-CO₂—C₁-C₆ alkyl, each of which is optionallysubstituted with 1, 2, 3, 4, or 5 groups that are independently alkyl,alkoxy, CO₂H, —CO₂-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy,hydroxyalkyl, alkanoyl, NO₂, CN, alkoxycarbonyl, or aminocarbonyl;

[0036] X is selected from the group consisting of —C₁-C₆ alkylidenyloptionally optionally substituted with 1, 2, or 3 methyl groups; and—NR₄₋₆—; or

[0037] R₄ and R₄₋₆ combine to form —(CH₂)_(n10)—, wherein

[0038] n₁₀ is 1, 2, 3, or 4;

[0039] Z is selected from the group consisting of a bond; SO₂; SO; S;and C(O);

[0040] Y is selected from the group consisting of H; C₁-C₄ haloalkyl;C₅-C₆ heterocycloalkyl; C₆-C₁₀ aryl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from the group consisting of halogen,hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C₃-C₈ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from C₁-C₃alkyl, and halogen; alkoxy; aryl optionally substituted with halogen,alkyl, alkoxy, CN or NO₂; arylalkyl optionally substituted with halogen,alkyl, alkoxy, CN or NO₂; wherein

[0041] Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0042] Y₁, Y₂ and the nitrogen to which they are attached form a ringselected from the group consisting of piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen;

[0043] R₁ is —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl), or

[0044] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, OH, ═O, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino, —N(R)C(O)R′—, —OC(═O)-amino and—OC(═O)-mono- or dialkylamino, or

[0045] C₂-C₆ alkenyl or C₂-C₆ alkynyl, each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, and mono- or dialkylamino, or

[0046] aryl, heteroaryl, heterocyclyl, —C₁-C₆ alkyl-aryl, —C₁-C₆alkyl-heteroaryl, or —C₁-C₆ alkyl-heterocyclyl, where the ring portionsof each are optionally substituted with 1, 2, 3, or 4 groupsindependently selected from halogen, —OH, —SH, —C≡N, —NR₁₀₅R′₁₀₅, —CO₂R,—N(R)COR′, or —N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono ordialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino,—SO₂—(C₁-C₄)alkyl, or

[0047] —C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently a halogen, or

[0048] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —CN, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0049] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0050] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and

[0051] the heterocyclyl group is optionally further substituted withoxo;

[0052] R and R′ independently are hydrogen or C₁-C₁₀ alkyl;

[0053] R₂ is selected from the group consisting of H; C₁-C₆ alkyl,optionally substituted with 1, 2, or 3 substituents that areindependently selected from the group consisting of C₁-C₃ alkyl,halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b);wherein R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; —(CH₂)₀₋₄-aryl;—(CH₂)₀₋₄-heteroaryl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; —CONR_(N-2)R_(N-3);—SO₂NR_(N-2)R_(N-3); —CO₂H; and —CO₂—(C₁-C₄ alkyl);

[0054] R₃ is selected from the group consisting of H; C₁-C₆ alkyl,optionally substituted with 1, 2, or 3 substituents independentlyselected from the group consisting of C₁-C₃ alkyl, halogen, —OH, —SH,—C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b); —(CH₂)₀₋₄-aryl;—(CH₂)₀₋₄-heteroaryl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; —CO—NR_(N-2)R_(N-3);—SO₂—NR_(N-2)R_(N-3); —CO₂H; and —CO—O—(C₁-C₄ alkyl); or

[0055] R₂, R₃ and the carbon to which they are attached form acarbocycle of three thru seven carbon atoms, wherein one carbon atom isoptionally replaced by a group selected from —O—, —S—, —SO₂—, or—NR_(N-2)—;

[0056] R_(C) is selected from the group consisting of C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂(C₁-C₆alkyl), —SH, —NR₂₃₅C═ONR₂₃₅R₂₄₀, —C═ONR₂₃₅R₂₄₀, and —S(═O)₂NR₂₃₅R₂₄₀;—(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl is optionallysubstituted with 1, 2, or 3 groups independently selected from the groupconsisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl; —(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-aryl-heteroaryl; —(CR₂₄₅R₂₅₀)₀₋₄-aryl-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-aryl-aryl; —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-aryl; —[C(R₂₅₅)(R₂₆₀)]₁₋₃—CO—N—(R₂₅₅)₂; —CH(aryl)₂; —CH(heteroaryl)₂;—CH(heterocycloalkyl)₂; —CH(aryl)(heteroaryl); cyclopentyl, cyclohexyl,or cycloheptyl ring fused to aryl, heteroaryl, or heterocycloalkylwherein one carbon of the cyclopentyl, cyclohexyl, or cycloheptyl isoptionally replaced with NH, NR₂₁₅, O, or S(═O)₀₋₂, and wherein thecyclopentyl, cyclohexyl, or cycloheptyl group can be optionallysubstituted with 1 or 2 groups that are independently R₂₀₅ or ═O;—CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); C₂-C₁₀ alkenyl optionally substitutedwith 1, 2, or 3 R₂₀₅ groups; C₂-C₁₀ alkynyl optionally substituted with1, 2, or 3 R₂₀₅ groups; —(CH₂)₀₋₁—CH((CH₂)₀₋₆—OH)—(CH₂)₀₋₁-aryl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(-aryl or-heteroaryl)-CO—O(C₁-C₄ alkyl); —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂; (C₁-C₆alkyl)-O—(C₁-C₆ alkyl)-OH; —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂; —H; and—(CH₂)₀₋₆—C(═NR₂₃₅) (NR₂₃₅R₂₄₀); wherein

[0057] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0058] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0059] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0060] R₂₀₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; OH; —NO₂; halogen; —CO₂H; C≡N; —(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅;—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl);—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl); —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl);—(CH₂)₀₋₄—CO-aryl; —(CH₂)₀₋₄—CO-heteroaryl;—(CH₂)₀₋₄—CO-heterocycloalkyl; —(CH₂)₀₋₄—CO₂R₂₁₅;—(CH₂)₀₋₄—SO₂—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl); —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl); —(CH₂)₀₋₄—N(H orR₂₁₅)—CO₂R₂₁₅; —(CH₂)₀₋₄—N(H or R₂₁₅)—CO—N(R₂₁₅)₂;—(CH₂)₀₋₄—N—CS—N(R₂₁₅)₂; —(CH₂)₀₋₄—N(—H or R₂₁₅)—CO—R₂₂₀;—(CH₂)₀₋₄—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl); —(CH₂)₀₋₄OP(O)—(OR₂₄₀)₂; —(CH₂)₀₋₄—O—CO—N(R₂₁₅)₂; —(CH₂)₀₋₄—O—CS—N(R₂₁₅)₂;—(CH₂)₀₋₄—O—(R₂₁₅)₂; —(CH₂)₀₋₄—O—(R₂₁₅)₂—COOH; —(CH₂)₀₋₄—S—(R₂₁₅)₂;—(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 5-F);C₃-C₇ cycloalkyl; C₂-C₆ alkenyl optionally substituted with 1 or 2 R₂₀₅groups; C₂-C₆ alkynyl optionally substituted with 1 or 2 R₂₀₅ groups;—(CH₂)₀₋₄—N(H or R₂₁₅)—SO₂—R₂₂₀; and —(CH₂)₀₋₄—C₃-C₇ cycloalkyl;

[0061] wherein each aryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀ orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0062] wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 groups that are independentlyR₂₁₀;

[0063] wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀, orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0064] R₂₀₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF₃,C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), and N-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0065] R₂₁₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; C₂-C₆ alkenyl optionally substituted with 1, 2, or 3 R₂₀₅groups; C₂-C₆ alkynyl optionally substituted with 1, 2, or 3 R₂₀₅groups; halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N;C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—CO—(C₁-C₄ alkyl); SO₂—NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and═O; wherein

[0066] R₂₁₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, —(CH₂)₀₋₂-(aryl), C₂-C₆ alkenyl, C₂-C₆alkynyl, C₃ -C₇ cycloalkyl, and —(CH₂)₀₋₂-(heteroaryl),—(CH₂)₀₋₂-(heterocycloalkyl); wherein the aryl group at each occurrenceis optionally substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀; wherein the heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 R₂₁₀; wherein each heteroarylgroup at each occurrence is optionally substituted with 1, 2, or 3 R₂₁₀;

[0067] R₂₂₀ and R₂₂₅ at each occurrence are independently selected fromthe group consisting of —H, —C₁-C₆ alkyl, hydroxy C₁-C₆ alkyl, aminoC₁-C₆ alkyl; halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇cycloalkyl), —(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl), —C₂-C₆ alkenyl, —C₂-C₆alkynyl, —CL-C₆ alkyl chain with one double bond and one triple bond,-aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group ateach occurrence is optionally substituted with 1, 2, or 3 R₂₇₀ groups,wherein

[0068] R₂₇₀ at each occurrence is independently R₂₀₅, C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkenyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkynyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆alkoxy; C₁-C₆ haloalkoxy; NR₂₃₅R₂₄₀; OH; C≡N; C₃-C₇ cycloalkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; —CO—(C₁-C₄ alkyl);SO₂—NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and ═O; wherein theheterocycloalkyl group at each occurrence is optionally substituted with1, 2, or 3 R₂₀₅ groups; wherein each heteroaryl group at each occurrenceis optionally substituted with 1, 2, or 3 R₂₀₅ groups;

[0069] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0070] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromthe group consisting of H, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl, aryl C₁-C₄ alkyl, heteroaryl C₁-C₄ alkyl, and phenyl; or

[0071] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms,optionally where one carbon atom is replaced by a heteroatom selectedfrom the group consisting of —O—, —S—, —SO₂—, and —NR₂₂₀—;

[0072] R₂₅₅ and R₂₆₀ at each occurrence are independently selected fromthe group consisting of H; C₁-C₆ alkyl optionally substituted with 1, 2,or 3 R₂₀₅ groups; C₂-C₆ alkenyl optionally substituted with 1, 2, or 3R₂₀₅ groups; C₂-C₆ alkynyl optionally substituted with 1, 2, or 3 R₂₀₅groups; —(CH₂)₁₂—S(O)₀₋₂—(C₁-C₆ alkyl); —(CH₂)₀₋₄—C₃-C₇ cycloalkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; —(C₁-C₄ alkyl)-aryl;—(C₁-C₄ alkyl)-heteroaryl; —(C₁-C₄ alkyl)-heterocycloalkyl; -aryl;-heteroaryl; -heterocycloalkyl; (CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-aryl;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heteroaryl; and;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heterocycloalkyl; wherein

[0073] R₂₆₅ at each occurrence is independently —O—, —S— or —N(C₁-C₆alkyl)-;

[0074] each aryl or phenyl is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅, R₂₁₀, or C₁-C₆ alkyl substitutedwith 1, 2, or 3 groups that are independently R₂₀₅ or R₂₁₀;

[0075] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀, each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4R₂₁₀;

[0076] R₁₀₀ and R′₁₀₀ independently represent aryl, heteroaryl,heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl,-heteroaryl-W-aryl, -heteroaryl-W-heteroaryl,-heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl,-heterocyclyl-w-heteroaryl, -heterocyclyl-W-heterocyclyl,—CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-aryl,—CH[(CH₂)₀₋₂—O—R₁₁₀]—(CH₂)₀₋₂-heterocyclyl or —CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-heteroaryl, where the ring portions of eachare optionally substituted with 1, 2, or 3 groups independently selectedfrom

[0077] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR′), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₅₀′—COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, and (C₂-C₁₀)alkynyl, or

[0078] R₁₀₀ is C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 R₁₁₅groups, or

[0079] R₁₀₀ is —(C₁-C₆ alkyl)-O—C₁-C₆ alkyl) or —(C₁-C₆ alkyl)-S—(C₁-C₆alkyl), each of which is optionally substituted with 1, 2, or 3 R₁₁₅groups, or

[0080] R₁₀₀ is C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3R₁₁₅ groups;

[0081] W is —(CH₂)₀₋₄—O——S(O)₀₋₂—, —N(R₁₃₅)—, —CR(OH)— or —C(O)—;

[0082] R₁₀₂ and R₁₀₂′ independently are hydrogen, or

[0083] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groups thatare independently halogen, aryl or —R₁₁₀;

[0084] R₁₀₅ and R′₁₀₅ independently represent —H, —R₁₁₀, —R₁₂₀, C₃-C₇cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl), —(C₁-C₆ alkyl)-O—(C₁-C₃alkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆ alkyl chain with onedouble bond and one triple bond, or

[0085] C₁-C₆ alkyl optionally substituted with —OH or —NH₂; or,

[0086] C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, or

[0087] R₁₀₅ and R′₁₀₅ together with the atom to which they are attachedform a 3 to 7 membered carbocylic ring, where one member is optionally aheteratom selected from —O—, —S(O)₀₋₂—, —N(R₁₃₅)—, the ring beingoptionally substituted with 1, 2 or 3 independently selected R₁₄₀groups;

[0088] R₁₁₅ at each occurrence is independently halogen, —OH, —CO₂R₁₀₂,—C₁-C₆ thioalkoxy, —CO₂-phenyl, —NR₁₀₅R′₁₀₅, —SO₂—(C₁-C₈ alkyl),—C(═O)R₁₈₀, R₁₈₀, —CONR₁₀₅R′₁₀₅, —SO₂NR₁₀₅R′₁₀₅, —NH—CO—(C₁-C₆ alkyl),—NH—C(═O)—OH, —NH—C(═O)—OR, —NH—C(═O)—O-phenyl, —O—C(═O)—(C₁-C₆ alkyl),—O—C(═O)-amino, —O—C(═O)-mono- or dialkylamino, —O—C(═O)-phenyl,—O—(C₁-C₆ alkyl)-CO₂H, —NH—SO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy or C₁-C₆haloalkoxy;

[0089] R₁₃₅ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₇cycloalkyl, —(CH₂)₀₋₂-(aryl), —(CH₂)₀₋₂-(heteroaryl), or—(CH₂)₀₋₂-(heterocyclyl);

[0090] R₁₄₀ is heterocyclyl optionally substituted with 1, 2, 3, or 4groups independently selected from C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen,hydroxy, cyano, nitro, amino, mono (C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl,di(C₁-C₆)alkylamino(C₁-C₆)alkyl, and ═O;

[0091] R₁₄₅ is C₁-C₆ alkyl or CF₃;

[0092] R₁₅₀ is hydrogen, C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇cycloalkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one doublebond and one triple bond, —R₁₁₀, —R₁₂₀, or

[0093] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, R₁₁₀, and halogen;

[0094] R₁₅₀′ is C₃-C₇ cycloalkyl, —(C₁-C₃ alkyl)-(C₃-C₇ cycloalkyl),C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one double bond and onetriple bond, —R₁₁₀, —R₁₂₀, or

[0095] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, R₁₁₀, and halogen;

[0096] R₁₅₅ is C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl),C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one double bond and onetriple bond, —R₁₁₀, —R₁₂₀, or

[0097] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, and halogen;

[0098] R₁₈₀ is selected from morpholinyl, thiomorpholinyl, piperazinyl,piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinylS-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl,each of which is optionally substituted with 1, 2, 3, or 4 groupsindependently selected from C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy,cyano, nitro, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy,amino(C₁-C₆)alkyl, mono (C₁-C₆)alkylamino (C₁-C₆)alkyl,di(C₁-C₆)alkylamino(C₁-C₆)alkyl, and ═O;

[0099] R₁₁₀ is aryl optionally substituted with 1 or 2 R₁₂₅ groups;

[0100] R₁₂₅ at each occurrence is independently halogen, amino, mono- ordialkylamino, —OH, —C≡N, —SO₂—NH₂, —SO₂—NH—C₁-C₆ alkyl, —SO₂—N(C₁-C₆alkyl)₂, —SO₂—(C₁-C₄ alkyl), —CO—NH₂, —CO—NH—C₁-C₆ alkyl, or —CO—N(C₁-C₆alkyl)₂, or

[0101] C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl, each of which isoptionally substituted with 1, 2, or 3 groups that are independentlyselected from C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, and mono- and dialkylamino, or

[0102] C₁-C₆ alkoxy optionally substituted with one, two or three ofhalogen;

[0103] R₁₂₀ is heteroaryl, which is optionally substituted with 1 or 2R₁₂₅ groups; and

[0104] R₁₃₀ is heterocyclyl optionally substituted with 1 or 2 R₁₂₅groups.

[0105] The invention also provides compounds of the formula I:

[0106] and pharmaceutically acceptable salts thereof, wherein R₁, R₂,R₃, and R_(C) are as defined for formula (AA), and

[0107] R_(N) is —C(═O)—(CRR′)₀₋₆R₁₀₀, —C(═O)—(CRR′)₁₋₆—O—R′₁₀₀,—C(═O)—(CRR′)₁₋₆—S—R′₁₀₀, —C(═O)—(CRR′)₁₋₆—C(═O)—R₁₀₀,—C(═O)—(CRR′)₁₋₆—SO₂—R₁₀₀, —C(═O)—(CRR′)₁₋₆—NR₁₀₀—R′₁₀₀, or

[0108] R_(N) is

[0109] wherein

[0110] R₄ is selected from the group consisting of H; NH₂;—NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; C₁-C₄ alkyl-NHC(O)R₅;—(CH₂)₀₋₄R₈; —O—C₁-C₄ alkanoyl; OH; C₆-C₁₀ aryloxy optionallysubstituted with 1, 2, or 3 groups that are independently halogen, C₁-C₄alkyl, —CO₂H, —C(O)—C₁-C₄ alkoxy, or C₁-C₄ alkoxy; C₁-C₆ alkoxy; arylC₁-C₄ alkoxy; —NR₅₀CO₂R₅₁; —C₁-C₄ alkyl-NR₅₀CO₂R₅₁; —C≡N; —CF₃;—CF₂—CF₃; —C═CH; —CH₂—CH═CH₂; —(CH₂)₁₋₄—R₄₋₁; —(CH₂)₁₄—NH—R₄₋₁;—O—(CH₂)_(n6)—R₄₋₁; —S—(CH₂)_(n6)—R₄₋₁; —(CH₂)₀₋₄—NHC(O)—(CH₂)₀₋₆—R₅₂;—(CH₂)₀₋₄—R₅₃—(CH₂)₀₋₄—R₅₄;

[0111] wherein

[0112] n₆ is 0, 1, 2, or 3;

[0113] n₇ is 0, 1, 2, or 3;

[0114] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0115] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0116] R₄₋₄ is alkyl, arylalkyl, alkanoyl, or arylalkanoyl;

[0117] R₄₋₆ is —H or C₁-C₆ alkyl;

[0118] R₅ is selected from the group consisting of C₃-C₇ cycloalkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆ heterocycloalkyl,C₅-C₆ heteroaryl, C₆-C₁₀ aryl, C₃-C₇ cycloalkyl C₁-C₄ alkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, C₆-C₁₀aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that areindependently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0119] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, phenyl C₁-C₄alkyl;

[0120] R₈ is selected from the group consisting of —SO₂-heteroaryl,—SO₂-aryl, —SO₂-heterocycloalkyl, —SO₂—C₁-C₁₀ alkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₁-C₆ alkyl, —S—C₂-C₄ alkanoyl, wherein

[0121] R₉ is aryl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl;

[0122] R₅₁ is selected from the group consisting of aryl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, heteroaryl, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇cycloalkyl, or —C₁-C₄ alkoxy; heterocycloalkyl optionally substitutedwith 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, C₂-C₄ alkanoyl, aryl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl;alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3groups that are independently OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); heteroarylalkyloptionally substituted with 1, 2, or 3 groups that are independentlyC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆alkyl)(C₁-C₆ alkyl); aryl; heterocycloalkyl; C₃-C₈ cycloalkyl; andcycloalkylalkyl; wherein the aryl; heterocycloalkyl, C₃-C₈ cycloalkyl,and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or5 groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy;

[0123] R₅₂ is heterocycloalkyl, heteroaryl, aryl, cycloalkyl,—S(O)₀₋₂—C₁-C₆ alkyl, CO₂H, —C(O)NH₂, —C(O)NH(alkyl),—C(O)N(alkyl)(alkyl), —CO₂-alkyl, —NHS(O)₀₋₂—C₁-C₆ alkyl,—N(alkyl)S(O)₀₋₂—C₁-C₆ alkyl, —S(O)₀₋₂-heteroaryl, —S(O)₀₋₂-aryl,—NH(arylalkyl), —N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each ofwhich is optionally substituted with 1, 2, 3, 4, or 5 groups that areindependently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy,alkanoyl, NO₂, CN, alkoxycarbonyl, or aminocarbonyl;

[0124] R₅₃ is absent, —O—, —C(O)—, —NH—, —N(alkyl)-, —NH—S(O)₀₋₂—,—N(alkyl)-S(O)₀₋₂—, —S(O)₀₋₂—NH—, —S(O)O₀₋₂—N(alkyl)-, —NH—C(S)—, or—N(alkyl)-C(S)—;

[0125] R₅₄ is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO₂H,—CO₂-alkyl, —C(O)NH(alkyl), —C(O)N(alkyl) (alkyl), —C(O)NH₂, C₁-C₈alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH₂, NH(alkyl), N(alkyl)(alkyl), or —C₁-C₆ alkyl-CO₂—C₁-C₆ alkyl, each of which is optionallysubstituted with 1, 2, 3, 4, or 5 groups that are independently alkyl,alkoxy, CO₂H, —CO₂-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy,hydroxyalkyl, alkanoyl, NO₂, CN, alkoxycarbonyl, or aminocarbonyl;

[0126] X is selected from the group consisting of —C₁-C₆ alkylidenyloptionally optionally substituted with 1, 2, or 3 methyl groups; and—NR₄₋₆—; or R₄ and R₄₋₆ combine to form —(CH₂)_(n10)—, wherein

[0127] n₁₀ is 1, 2, 3, or 4;

[0128] Z is selected from the group consisting of a bond; SO₂; SO; S;and C(O);

[0129] Y is selected from the group consisting of H; C₁-C₄ haloalkyl;CS—C₆ heterocycloalkyl; C₆-C₁₀ aryl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from the group consisting of halogen,hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C₃-C₈ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from C₁-C₃alkyl, and halogen; alkoxy; aryl optionally substituted with halogen,alkyl, alkoxy, CN or NO₂; arylalkyl optionally substituted with halogen,alkyl, alkoxy, CN or NO₂; wherein

[0130] Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0131] Y₁, Y₂ and the nitrogen to which they are attached form a ringselected from the group consisting of piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen; R₁₀₀ andR′₁₀₀ independently represent aryl, heteroaryl, heterocyclyl,-aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl,-heteroaryl-W-aryl, -heteroaryl-W-heteroaryl,-heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl,-heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl,—CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-aryl,—CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-heterocyclyl or —CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-heteroaryl, where the ring portions of eachare optionally substituted with 1, 2, or 3 groups independently selectedfrom

[0132] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃, —(CH₂)o-4-O—P(═O)(OR)(OR′), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀O,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₅₀—COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, and (C₂-C₁₀)alkynyl, or

[0133] R₁₀₀ is C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 R₁₁₅groups, or

[0134] R₁₀₀ is —(C₁-C₆ alkyl)-O—C₁-C₆ alkyl) or —(C₁-C₆ alkyl)-S—(C₁-C₆alkyl), each of which is optionally substituted with 1, 2, or 3 R₁₁₅groups, or

[0135] R₁₀₀ is C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3R₁₁₅ groups;

[0136] W is —(CH₂)₀₋₄, —O—, S(O)₀₋₂, —N(R₁₃₅)—, —CR(OH)— or —C(O)—;

[0137] R₁₀₂ and R₁₀₂′ independently are hydrogen, or

[0138] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groups thatare independently halogen, aryl or —R₁₁₀;

[0139] R₁₀₅ and R′₁₀₅ independently represent —H, —R₁₁₀, —R₁₂₀, C₃-C₇cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl), —(C₁-C₆ alkyl)-O—(C₁-C₃alkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆ alkyl chain with onedouble bond and one triple bond, or

[0140] C₁-C₆ alkyl optionally substituted with —OH or —NH₂; or,

[0141] C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, or

[0142] R₁₀₅ and R′₁₀₅ together with the atom to which they are attachedform a 3 to 7 membered carbocylic ring, where one member is optionally aheteratom selected from —O—, —S(O)₀₋₂—, —N(R₁₃₅)—, the ring beingoptionally substituted with 1, 2 or 3 independently selected R₁₄₀groups;

[0143] R₁₁₅ at each occurrence is independently halogen, —OH, —CO₂R₁₀₂,—C₁-C₆ thioalkoxy, —CO₂-phenyl, —NR₁₀₅R′₁₃₅, —SO₂—(C₁-C₈ alkyl),—C(═O)R₁₈₀, R₁₈₀, —CONR₁₀₅R′₁₀₅, —SO₂NR₁₀₅R′₁₀₅, —NH—CO—(C₁-C₆ alkyl),—NH—C(═O)—OH, —NH—C(═O)—OR, —NH—C(═O)—O-phenyl, —O—C(═O)-(C_(1-C) ₆alkyl), —O—C(═O)-amino, —O—C(═O)-mono- or dialkylamino, —O—C(═O)-phenyl,—O—(C₁-C₆ alkyl)-CO₂H, —NH—SO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy or C₁-C₆haloalkoxy;

[0144] R₁₃₅ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₇cycloalkyl, —(CH₂)₀₋₂-(aryl), —(CH₂)₀₋₂-(heteroaryl), or—(CH₂)₀₋₂-(heterocyclyl);

[0145] R₁₄₀ is heterocyclyl optionally substituted with 1, 2, 3, or 4groups independently selected from C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen,hydroxy, cyano, nitro, amino, mono (C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl,di(C₁-C₆)alkylamino(C₁-C₆)alkyl, and ═O;

[0146] R₁₄₅ is C₁-C₆ alkyl or CF₃;

[0147] R₁₅₀ is hydrogen, C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇cycloalkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one doublebond and one triple bond, —R₁₁₀, —R₁₂₀, or

[0148] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, R₁₁₀, and halogen;

[0149] R₁₅₀′ is C₃-C₇ cycloalkyl, —(C₁-C₃ alkyl)-(C₃-C₇ cycloalkyl),C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one double bond and onetriple bond, —R₁₁₀, —R₁₂₀, or

[0150] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, R₁₁₀, and halogen;

[0151] R₁₅₅ is C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl),C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one double bond and onetriple bond, —R₁₁₀, —R₁₂₀, or

[0152] C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 4 groupsindependently selected from —OH, —NH₂, C₁-C₃ alkoxy, and halogen;

[0153] R₁₈₀ is selected from morpholinyl, thiomorpholinyl, piperazinyl,piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinylS-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl,each of which is optionally substituted with 1, 2, 3, or 4 groupsindependently selected from C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy,cyano, nitro, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy,amino(C₁-C₆)alkyl, mono (C₁-C₆)alkylamino (C₁-C₆)alkyl,di(C₁-C₆)alkylamino(C₁-C₆)alkyl, and ═O;

[0154] R₁₁₀ is aryl optionally substituted with 1 or 2 R₁₂₅ groups;

[0155] R₁₂₅ at each occurrence is independently halogen, amino, mono- ordialkylamino, —OH, —C≡N, —SO₂—NH₂, —SO₂—NH—C₁-C₆ alkyl, —SO₂—N(C₁-C₆alkyl)₂, —SO₂—(C₁-C₄ alkyl), —CO—NH₂, —CO—NH—C₁-C₆ alkyl, or —CO—N(C₁-C₆alkyl)₂, or

[0156] C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl, each of which isoptionally substituted with 1, 2, or 3 groups that are independentlyselected from C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, and mono- and dialkylamino, or

[0157] C₁-C₆ alkoxy optionally substituted with one, two or three ofhalogen;

[0158] R₁₂₀ is heteroaryl, which is optionally substituted with 1 or 2R₁₂₅ groups; and

[0159] R₁₃₀ is heterocyclyl optionally substituted with 1 or 2 R₁₂₅groups.

[0160] The invention also provides compounds of the formula X:

[0161] and pharmaceutically acceptable salts thereof, wherein R₁, R₂,R₃, R_(N) and R_(C) are as defined for formula (I).

[0162] The invention also provides methods of generating compounds offormula (Y) from the compounds of formulae (AA), (I) or (X):

[0163] wherein R₁, R₂, R₃, R_(N) and R_(C) are as defined for formula(I). The generation of compounds of formula (Y) from compounds offormulae (AA), (I) or (X) can occur in vivo or in vitro. Compounds offormula Y are useful for treating and/or preventing Alzheimer's disease.

[0164] The invention also provides processes for converting compounds offormula AA, I or X to the compounds of formula Y. The conversion and/orgeneration of compounds of formula Y involves contacting the compoundsof formula I and/or X with an aqueous medium. The conversion can occurin vitro or in vivo.

[0165] The invention also provides methods for the treatment orprevention of Alzheimer's disease, mild cognitive impairment Down'ssyndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of theDutch-Type, cerebral amyloid angiopathy, other degenerative dementias,dementias of mixed vascular and degenerative origin, dementia associatedwith Parkinson's disease, dementia associated with progressivesupranuclear palsy, dementia associated with cortical basaldegeneration, diffuse Lewy body type of Alzheimer's disease compriseingadministration of a therapeutically effective amount of a compound orsalt of formula AA, I or X, to a patient in need thereof.

[0166] Preferably, the patient is a human.

[0167] More preferably, the disease is Alzheimer's disease.

[0168] More preferably, the disease is dementia.

[0169] The invention also provides pharmaceutical compositionscomprising a compound or salt of formula AA, I or X and at least onepharmaceutically acceptable carrier, solvent, adjuvant or diluent.

[0170] The invention also provides the use of a compound or saltaccording to formula AA, I or X for the manufacture of a medicament.

[0171] The invention also provides the use of a compound or salt offormula (AA), formula (I) or formula (X) for the treatment or preventionof Alzheimer's disease, mild cognitive impairment Down's syndrome,Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type,cerebral amyloid angiopathy, other degenerative dementias, dementias ofmixed vascular and degenerative origin, dementia associated withParkinson's disease, dementia associated with progressive supranuclearpalsy, dementia associated with cortical basal degeneration, or diffuseLewy body type of Alzheimer's disease.

[0172] The invention also provides compounds, pharmaceuticalcompositions, kits, and methods for inhibiting beta-secretase-mediatedcleavage of amyloid precursor protein (APP). More particularly, thecompounds, compositions, and methods of the invention are effective toinhibit the production of A-beta peptide and to treat or prevent anyhuman or veterinary disease or condition associated with a pathologicalform of A-beta peptide.

[0173] The invention also provides methods of preparing the compounds ofthe invention and the intermediates used in those methods.

[0174] The compounds, compositions, and methods of the invention areuseful for treating humans who have Alzheimer's Disease (AD), forhelping prevent or delay the onset of AD, for treating patients withmild cognitive impairment (MCI), and preventing or delaying the onset ofAD in those patients who would otherwise be expected to progress fromMCI to AD, for treating Down's syndrome, for treating HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch Type, for treatingcerebral beta-amyloid angiopathy and preventing its potentialconsequences such as single and recurrent lobar hemorrhages, fortreating other degenerative dementias, including dementias of mixedvascular and degenerative origin, for treating dementia associated withParkinson's disease, dementia associated with progressive supranuclearpalsy, dementia associated with cortical basal degeneration, and diffuseLewy body type AD, and for treating frontotemporal dementias withparkinsonism (FTDP).

[0175] The compounds of formula Y possess beta-secretase inhibitoryactivity. The inhibitory activities of the compounds of the invention isreadily demonstrated, for example, using one or more of the assaysdescribed herein or known in the art.

[0176] Unless the substituents for a particular formula are expresslydefined for that formula, they are understood to carry the definitionsset forth in connection with the preceding formula to which theparticular formula makes reference.

DETAILED DESCRIPTION OF THE INVENTION

[0177] As noted above, the invention provides compounds of formulae(AA), (I) and (X) that are useful in the treatment and prevention ofAlzheimer's disease. These compounds can be viewed as prodrugs of theactive compounds of Formula Y since they generate the active compoundboth in vivo and in vitro.

[0178] The compounds of formula AA, I and X undergo acyl group migrationof the R_(N) group when in contact with water, as depicted in Scheme I.The migration associated with compounds of formula (I) is referred toherein as “N-acyl migration.” The migration associated with compounds offormula (X) is referred to herein as “O-acyl migration.”

[0179] The migrations depicted in SCHEME 1 can occur either in vitro orin vivo and occur when the compounds are contacted with aqueous media,including water itself. The aqueous medium can be neutral, acidic orbasic. It is preferred that the media have a pH of about 2 to about 10,more preferably, about 3 to about 7. The amount of water required forthe migration is not critical. A catalytic amount of aqueous media willsuffice to cause the migration. Aqueous buffer solutions as well asgastric fluid are satisfactory media for the migration to occur.

[0180] The products of the rearrangements of the compounds of formulaAA, formula I and/or formula X are the compounds of formula (Y). Thesubstituents R₁, R₂, R₃, R_(N) and R_(C) in the compounds (Y) are asdefined above for compounds of formula (I).

[0181] Preferred compounds of formula AA include those of formula AA-1,i.e., compounds of formula AA wherein

[0182] R₁ is aryl, heteroaryl, heterocyclyl, —C₁-C₆ alkyl-aryl, —C₁-C₆alkyl-heteroaryl, or —C₁-C₆ alkyl-heterocyclyl, where the ring portionsof each are optionally substituted with 1, 2, 3, or 4 groupsindependently selected from halogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅,—CO₂R, —N(R)COR′, or —N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino,—SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino,—SO₂—(C₁-C₄) alkyl, or

[0183] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0184] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0185] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0186] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0187] Preferred compounds of formula AA-1 also include those wherein

[0188] R₁ is —C₁-C₆ alkyl-aryl, —C₁-C₆ alkyl-heteroaryl, or —C₁-C₆alkyl-heterocyclyl, where the ring portions of each are optionallysubstituted with 1, 2, 3, or 4 groups independently selected fromhalogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or—N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono or dialkylamino,—C(═O)amino, —C(═O)-mono or dialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0189] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0190] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0191] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0192] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0193] Preferred compounds of formula AA-1 further include those wherein

[0194] R₁ is —(CH₂)-aryl, —(CH₂)-heteroaryl, or —(CH₂)-heterocyclyl,where the ring portions of each are optionally substituted with 1, 2, 3,or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO₂,—NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or —N(R)SO₂R, —C(═O)—(C₁-C₄)alkyl,—SO₂-amino, —SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono ordialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0195] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0196] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0197] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0198] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0199] Preferred compounds of formula AA-1 also include those wherein

[0200] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the ring portions ofeach are optionally substituted with 1, 2, 3, or 4 groups independentlyselected from halogen, C₁-C₄ alkoxy, hydroxy, —NO₂, and

[0201] C₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituentsindependently selected from halogen, OH, SH, NH₂, NH(C₁-C₆ alkyl),N-(C₁-C₆ alkyl)(C₁-C₆ alkyl), C≡N, CF₃.

[0202] Preferred compounds of formula AA-1 further include those wherein

[0203] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the phenyl or pyridinylrings are each optionally substituted with 1 or 2 groups independentlyselected from halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, hydroxy, —CF₃, and—NO₂.

[0204] Preferred compounds of formula AA-1 include those wherein

[0205] R₁ is —CH₂-phenyl where the phenyl ring is optionally substitutedwith 2 groups independently selected from halogen, C₁-C₂ alkyl, C₁-C₂alkoxy, hydroxy, and —NO₂.

[0206] Preferred compounds of formula AA-1 also include those wherein R₁is benzyl, or 3,5-difluorobenzyl.

[0207] Preferred compounds of formula AA and AA-1 include those offormula AA-2, i.e., compounds of formula AA or AA-1 wherein

[0208] R₂ and R₃ are independently selected from H or C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃alkoxy, and —NR_(1-a)R_(1-b).

[0209] Preferred compounds of formula AA-2 include those wherein

[0210] R_(C) is selected from the group consisting of C₁-C₃₀ alkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂(C₁-C₆alkyl), —SH, —NR₂₃₅C═ONR₂₃₅R₂₄₀, —C═ONR₂₃₅R₂₄₀, and —S(═O)₂NR₂₃₅R₂₄₀;—(CH₂)₀₋₃—(C₃-C₈)cycloalkyl wherein the cycloalkyl is optionallysubstituted with 1, 2, or 3 groups independently selected from the groupconsisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl; —(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl; —[C(R₂₅₅)(R₂₆₀)]₁₃—CO—N—(R₂₅₅)₂; —CH(aryl)₂; —CH(heteroaryl)₂;—CH(heterocycloalkyl)₂; —CH (aryl)(heteroaryl); —CO—NR₂₃₅R₂₄₀;—(CH₂)₀₋₁—CH((CH₂)₀₋₆—OH)—(CH₂)₀₋₁-aryl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(-aryl or-heteroaryl)-CO—O(C₁-C₄ alkyl); —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂; (C₁-C₆alkyl)-O—(C₁-C₆ alkyl)-OH; —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂; —H; and—(CH₂)₀₋₆—C(═NR₂₃₅) (NR₂₃₅R₂₄₀); wherein

[0211] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0212] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0213] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0214] R₂₀₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; OH; —NO₂; halogen; —CO₂H; C≡N; —(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅;—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅; and —(CH₂)₀₋₄—O—(C₁-C₆alkyl optionally substituted with 1, 2, 3, or 5-F);

[0215] wherein each aryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀ orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0216] wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 groups that are independentlyR₂₁₀;

[0217] wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀, orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0218] R₂₀₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF₃,C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), and N-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0219] R₂₁₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N;C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and═O; wherein

[0220] R₂₁₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, —(CH₂)₀₋₂—(aryl), C₃-C₇ cycloalkyl, and—(CH₂)₀₋₂-(heteroaryl), —(CH₂)₀₋₂-(heterocycloalkyl); wherein the arylgroup at each occurrence is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅ or R₂₁₀; wherein the heterocycloalkylgroup at each occurrence is optionally substituted with 1, 2, or 3 R₂₁₀;wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₁₀;

[0221] R₂₂₀ and R₂₂₅ at each occurrence are independently selected fromthe group consisting of —H, —C₁-C₆ alkyl, hydroxy C₁-C₆ alkyl, aminoC₁-C₆ alkyl; halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, —(C₁-C₆alkyl)-O—(C₁-C₃ alkyl), -aryl, -heteroaryl, and -heterocycloalkyl;wherein the aryl group at each occurrence is optionally substituted with1, 2, or 3 R₂₇₀ groups, each heteroaryl is optionally substituted with1, 2, 3, or 4 R₂₀₀, each heterocycloalkyl is optionally substituted with1, 2, 3, or 4 R₂₁₀ wherein

[0222] R₂₇₀ at each occurrence is independently R₂₀₅, C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆alkoxy; C₁-C₆ haloalkoxy; NR₂₃₅R₂₄₀; OH; C≡N; —CO—(C₁-C₄ alkyl); and ═O;wherein the heterocycloalkyl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; wherein each heteroaryl groupat each occurrence is optionally substituted with 1, 2, or 3 R₂₀₅groups;

[0223] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0224] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromthe group consisting of H, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, or

[0225] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms,wherein the carbocycle is optionally substituted with 1 or 2 groups thatare independently OH, methyl, Cl, F, OCH₃, CF₃, NO₂, or CN;

[0226] R₂₅₅ and R₂₆₀ at each occurrence are independently selected fromthe group consisting of H; C₁-C₆ alkyl optionally substituted with 1, 2,or 3 R₂₀₅ groups; —(CH₂)₀₋₄—C₃-C₇ cycloalkyl optionally substituted with1, 2, or 3 R₂₀₅ groups; —(C₁-C₄ alkyl)-aryl; —(C₁-C₄ alkyl)-heteroaryl;—(C₁-C₄ alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-aryl; —(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heteroaryl; and;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heterocycloalkyl; wherein

[0227] R₂₆₅ at each occurrence is independently —O—, —S— or —N(C₁-C₆alkyl)-;

[0228] each aryl or phenyl is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅, R₂₁₀, or C₁-C₆ alkyl substitutedwith 1, 2, or 3 groups that are independently R₂₀₅ or R₂₁₀.

[0229] Preferred compounds of formula AA-2 include those wherein:

[0230] R_(C) is —(CR₂₄₅R₂₅₀)₀₋₄-aryl, or —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl,wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3R₂₀₀ groups.

[0231] Preferred compounds of formula AA-2 also include compoundswherein

[0232] R_(C) is —(CR₂₄₅R₂₅₀)-aryl, or —(CR₂₄₅R₂₅₀)-heteroaryl whereineach aryl and heteroaryl is optionally substituted with 1, 2, or 3 R₂₀₀groups.

[0233] Preferred compounds of formula AA-2 also include compoundswherein

[0234] R_(C) is —(CH₂)-aryl, or —(CH₂)-heteroaryl, wherein

[0235] each aryl and heteroaryl is optionally substituted with 1, 2, or3 groups selected from OH, —NO₂, halogen, —CO₂H, C═N,—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), and—(CH₂)₀₋₄—SO₂—NR₂₂₀R₂₂₅.

[0236] Preferred compounds of formula AA-2 also include compoundswherein

[0237] R_(C) is —(CH₂)-aryl, wherein aryl is optionally substituted with1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C≡N.

[0238] Preferred compounds of formula AA-2 also include compoundswherein

[0239] R_(C) is —(CH₂)-phenyl, wherein phenyl is optionally substitutedwith 1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C≡N.

[0240] Preferred compounds of formula AA-2 also include compoundswherein R_(C) is benzyl.

[0241] Other preferred compounds of formulas AA, AA-1 and AA-2 includecompounds of formula AA-3, i.e., those of formulas AA, AA-1 or AA-2wherein

[0242] one of R_(N) and R_(N)′ is hydrogen and the other is:

[0243] wherein

[0244] R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or—NR₅₀CO₂R₅₁;

[0245] wherein

[0246] n₆ is 0, 1, 2, or 3;

[0247] n₇ is 0, 1, 2, or 3;

[0248] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0249] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0250] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0251] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; and cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₀-C₆ alkyl), N(C₁-C₆alkyl)(C₀-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0252] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0253] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0254] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl;

[0255] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy.

[0256] Preferred compounds of formula AA-3 include compounds wherein

[0257] one of R_(N) and R_(N)′ is hydrogen and the other is

[0258] wherein

[0259] X is C₁-C₄ alkylidenyl optionally substituted with 1, 2, or 3methyl groups; or —NR₄₋₆—; or

[0260] R₄ and R₄₋₆ combine to form —(CH₂)_(n10)—, wherein

[0261] n₁₀ is 1, 2, 3, or 4;

[0262] Z is selected from a bond; SO₂; SO; S; and C(O);

[0263] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from halogen, hydroxy, alkoxy, thioalkoxy,and haloalkoxy; C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3groups independently selected from C₁-C₃ alkyl, and halogen; alkoxy;phenyl optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy,CN or NO₂; phenyl C₁-C₄ alkyl optionally substituted with halogen, C₁-C₄alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0264] Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; and C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0265] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0266] Preferred compounds of formula AA-3 include compounds wherein

[0267] X is C₁-C₄ alkylidenyl optionally optionally substituted with 1,2, or 3 methyl groups;

[0268] Z is selected from SO₂; SO; S; and C(O);

[0269] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from the group consisting of halogen,hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C₃-C₈ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from C₁-C₃alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen,C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; phenyl C₁-C₄ alkyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0270] Y₁ and Y₂ are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0271] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0272] Preferred compounds of formula AA-3 include compounds one ofR_(N) and R_(N)′ is hydrogen and the other is:

[0273] wherein R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or—NR₅₀CO₂R₅₁ wherein

[0274] n₆ is 0, 1, 2, or 3;

[0275] n₇ is 0, 1, 2, or 3;

[0276] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0277] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0278] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0279] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0280] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0281] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0282] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl; and

[0283] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy; and

[0284] Y is C₁-C₁₀ alkyl optionally substituted with 1 thru 3substituents which can be the same or different and are selected fromhalogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy.

[0285] Preferred compounds of formula AA-3 further include compoundswherein

[0286] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from the group consisting of R₂₀₅,—OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂(C₁-C₆ alkyl), —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl);—(CR₂₄₅R₂₅₀)₀₋₄-phenyl; —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl;—(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂;(C₁-C₆ alkyl)-O—(C₁-C₆ alkyl)-OH; or —(CH₂)₀₋₆—C(═NR₂₃₅)(NR₂₃₅R₂₄₀);wherein

[0287] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0288] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0289] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0290] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;or —(CH₂)_(0-—) ₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0291] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), orN—(C₁-C₆ alkyl)(C₀-C₆ alkyl);

[0292] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆ alkoxy; C₁-C₆haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N; C₃-C₇ cycloalkyl optionally substitutedwith 1, 2, or 3 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀;—CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0293] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂-(phenyl), C₃₋C₇ cycloalkyl, and —(CH₂)₀₋₂-(heteroaryl),—(CH₂)₀₋₂-(heterocycloalkyl); wherein the phenyl group at eachoccurrence is optionally substituted with 1, 2, or 3 groups that areindependently R₂₀₅ or R₂₁₀; wherein the heterocycloalkyl group at eachoccurrence is optionally substituted with 1, 2, or 3 R₂₁₀; wherein eachheteroaryl group at each occurrence is optionally substituted with 1, 2,or 3 R_(210;)

[0294] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₆alkyl, hydroxy C₁-C₆ alkyl, halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, and—(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl);

[0295] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0296] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0297] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms.

[0298] Preferred compounds of formula AA-3 include compounds wherein

[0299] R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4groups independently selected from halogen, C₁-C₄ alkoxy, hydroxy, andC₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituents halogen,OH, SH, NH₂, NH(C₁-C₆ alkyl), N-(C₁-C₆ alkyl)(C₁-C₆-alkyl), C—N, CF₃;

[0300] R₂ and R₃ are independently selected from H or C₁-C₄ alkyloptionally substituted with 1 substituent selected from halogen, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, NH₂, NH(C₁-C₆ alkyl), and NH(C₁-C₆alkyl)(C₁-C₆ alkyl);

[0301] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from R₂₀₅, —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃—(C₃-C₆) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-phenyloptionally substituted with 1, 2, or 3 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyridazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrimidinyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-furyl;—(CR₂₄₅R₂₅₀)₀₋₃-indolyl; —(CR₂₄₅R₂₅₀) O₃-thienyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrrolyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrazolyl;(CR₂₄₅R₂₅₀)₀₋₃-benzoxazolyl; —(CR₂₄₅R₂₅₀)₀₋₃-imidazolyl; each of theabove heteroaryl groups is optionally substituted with 1, 2, 3, or 4R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-imidazolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-tetrahydrofuryl;(CR₂₄₅R₂₅₀)₀₋₃-tetrahydropyranyl; (CR₂₄₅R₂₅₀)₀₋₃-piperazinyl;(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-piperidinyl;(CR₂₄₅R₂₅₀)₀₋₃-indolinyl; each of the above heterocycloalkyl groups isoptionally substituted with 1, 2, 3, or 4 R₂₁₀;(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl; —(CH₂)₀₋₁—CH(C₁-C₄hydroxyalkyl)-(CH₂)₀₋₁-pyridyl;

[0302] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₈ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;and —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0303] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), andN-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0304] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1 or 2 R₂₀₅ groups; halogen; C₃-C₄ alkoxy; C₁-C₄haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N; C₃-C₇ cycloalkyl optionally substitutedwith 1 or 2 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀;—SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0305] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂—(phenyl), C₃-C₆ cycloalkyl, —(CH₂)₀₋₂-(pyridyl),—(CH₂)₀₋₂—(pyrrolyl), —(CH₂)₀₋₂-(imidazolyl), —(CH₂)₀₋₂-(pyrimidyl),—(CH₂)₀₋₂-(pyrrolidinyl), —(CH₂)₀₋₂-(imidazolidinyl),—(CH₂)₀₋₂-(piperazinyl), —(CH₂)₀₋₂-(piperidinyl), and—(CH₂)₀₋₂-(morpholinyl); wherein the phenyl group at each occurrence isoptionally substituted with 1 or 2 groups that are independently R₂₀₅ orR₂₁₀; wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1 or 2 R₂₁₀; wherein each heteroaryl groupat each occurrence is optionally substituted with 1 or 2 R₂₁₀;

[0306] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₄alkyl, hydroxy C₁-C₄ alkyl, halo C₁-C₄ alkyl; —C₃-C₆ cycloalkyl, and—(C₁-C₄ alkyl)-O—(C₁-C₂ alkyl);

[0307] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0308] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0309] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, or 6 carbon atoms.

[0310] Other preferred compounds of formula AA-3 include compoundswherein

[0311] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1or 2 methyl groups;

[0312] Z is SO₂; SO; S; or C(O);

[0313] Y is C₁-C₄ haloalkyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, C₁-C₄ alkoxy, C₁-C₄ thioalkoxy,and C₁-C₄ haloalkoxy; C₁-C₄ alkoxy; phenyl optionally substituted withhalogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; and benzyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0314] Y₁ and Y₂ are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected fromhalogen, C₁-C₂ alkoxy, C₃-C₆ cycloalkyl, and OH; C₂-C₆ alkanoyl; phenyl;—SO₂—C₁-C₄ alkyl; benzyl; and C₃-C₆ cycloalkyl C₁-C₂ alkyl; or

[0315] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0316] Preferred compounds of formula AA-3 also include those of formulaAA-4, i.e., compounds of formula AA-3 wherein

[0317] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1methyl group;

[0318] Z is SO₂; SO; S; or C(O);

[0319] Y is OH; —N(Y₁)(Y₂); phenyl; benzyl; or C₁-C₁₀ alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy,thioethoxy, and CF₃; wherein

[0320] Y₁ and Y₂ are the same or different and are H; C₁-C₄ alkyloptionally substituted with 1 or 2 substituents selected from halogen,methoxy, ethoxy, cyclopropyl, and OH; or

[0321] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄alkoxy, or halogen;

[0322] R₁ is benzyl which is optionally substituted with 1, 2, or 3groups independently selected from methyl, ethyl, n-propyl, isopropyl,hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, —CH₂CF₃,methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, andOH;

[0323] R₂ and R₃ are independently H or C₁-C₄ alkyl;

[0324] R_(C) is C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl,cyclohexyl, cyclohexylmethyl; —(CR₂₄₅R₂₅₀)₀₋₃-phenyl optionallysubstituted with 1 or 2 R₂₀₀ groups; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl optionallysubstituted with 1 or 2 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-piperazinyl; or(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; —(CR₂₄₅R₂₅₀)₀₋₃-piperidinyl; each of theabove heterocycloalkyl groups is optionally substituted with 1 or 2 R₂₁₀groups;

[0325] R₂₀₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; OH; and halogen;

[0326] R₂₀₅ at each occurrence is independently selected from C₁-C₄alkyl, halogen, —OH, —SH, —C≡N, —CF₃, and C₁-C₄ alkoxy;

[0327] R₂₁₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; halogen; C₁-C₄alkoxy; OCF₃; NH₂, NH(C₁-C₆ alkyl); N(C₁-C₆ alkyl)(C₁-C₆ alkyl); OH; and—CO—(C₁-C₄ alkyl); wherein

[0328] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromH, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, or

[0329] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 5, or 6 carbon atoms.

[0330] Preferred compounds of formulas AA, AA-1 and AA-2 includecompounds of formula AA-5, i.e., those of formulae AA, AA-1 or AA-2wherein

[0331] one of R_(N) and R_(N)′ is hydrogen and the other is—C(═O)—(CRR′)₀₋₆R₁₀₀; and

[0332] R₁₀₀ represents aryl, heteroaryl, or heterocyclyl, where the ringportions of each are optionally substituted with 1, 2, or 3 groupsindependently selected from

[0333] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR′), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₅₀′—COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0334] Preferred compounds of formula AA-5 include compounds wherein

[0335] one of R_(N) and R_(N)′ is hydrogen and the other is —C(═O)—R₁₀₀;and

[0336] R₁₀₀ represents aryl, or heteroaryl, where the ring portions ofeach are optionally substituted with 1, 2, or 3 groups independentlyselected from

[0337] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR′), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀,—(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀, —(CH₂)₀O₄—CO—R₁₃₀,—(CH₂)₀O₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂ (C₁-C₁₂ alkyl),—(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅, —(CH₂)₀₋₄—NR₁₀₅R′₁₅₀, —(CH₂)₀₋₄—R₁₄₀,—(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), —(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀O₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀),—(CH₂)₀₋₄—O—R₁₅₀—COOH, —(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0338] Preferred compounds of formula AA-5 also include compoundswherein

[0339] one of R_(N) and R_(N)′ is hydrogen and the other is —C(═O)-arylor —C(═O)-heteroaryl where the ring portions of each are optionallysubstituted with 1, 2, or 3 groups independently selected from

[0340] —OR, —NO₂, C₁-C₆ alkyl, halogen, —CO≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′,—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl), —(CH₂)₀₋₄—R₁₁₀—(CH₂)₀₋₄—R₁₂₀,—(CH₂)₀₋₄—R₁₃₀—(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀—(CH₂)₀₋₄—CO—R₁₃₀,—(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₅₀—(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0341] Other preferred compounds of formula AA-5 include compoundswherein

[0342] one of R_(N) and R_(N)′ is hydrogen and the other is —C(═O)-arylor —C(═O)-heteroaryl where the ring portions of each are optionallysubstituted with 1 or 2 groups independently selected from

[0343] C₁-C₆ alkyl, halogen, —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl,—(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀) alkynyl.

[0344] Other preferred compounds of formula AA-5 include compoundswherein

[0345] one of R_(N) and R_(N)′ is hydrogen and the other is—C(═O)-phenyl, where the phenyl ring is optionally substituted with 1 or2 groups independently selected from

[0346] C₁-C₆ alkyl, halogen, —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)_(0-—)₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅,C₃-C₇ cycloalkyl, (C₂-C₁₀) alkenyl, —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀—(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀) alkynyl.

[0347] Other preferred compounds of formula AA-5 also include compoundswherein one of R_(N) and R_(N)′ is hydrogen and the other is:

[0348] wherein sub is hydrogen or is C₁-C₆ alkyl, halogen,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl,—(C₂-C₁₀)alkenyl, —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or(C₂-C₁₀)alkynyl.

[0349] A preferred stereochemistry for compounds of formula AA is asfollows:

[0350] Preferred compounds of formula I include those of formula I-1,i.e., compounds of formula I wherein

[0351] R₁ is aryl, heteroaryl, heterocyclyl, —C₁-C₆ alkyl-aryl, —C₁-C₆alkyl-heteroaryl, or —C₁-C₆ alkyl-heterocyclyl, where the ring portionsof each are optionally substituted with 1, 2, 3, or 4 groupsindependently selected from halogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅,—CO₂R, —N(R)COR′, or —N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino,—SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino,—SO₂—(C₁-C₄) alkyl, or

[0352] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0353] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0354] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0355] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0356] Preferred compounds of formula I-1 also include those wherein

[0357] R₁ is —C₁-C₆ alkyl-aryl, —C₁-C₆ alkyl-heteroaryl, or —C₁-C₆alkyl-heterocyclyl, where the ring portions of each are optionallysubstituted with 1, 2, 3, or 4 groups independently selected fromhalogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or—N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono or dialkylamino,—C(═O)-amino, —C(═O)-mono or dialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0358] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0359] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0360] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0361] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0362] Preferred compounds of formula I-1 further include those wherein

[0363] R₁ is —(CH₂)-aryl, —(CH₂)-heteroaryl, or —(CH₂)-heterocyclyl,where the ring portions of each are optionally substituted with 1, 2, 3,or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO₂,—NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or —N(R)SO₂R, —C(═O)—(C₁-C₄)alkyl,—SO₂-amino, —SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono ordialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0364] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0365] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0366] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0367] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0368] Preferred compounds of formula I-1 also include those wherein

[0369] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the ring portions ofeach are optionally substituted with 1, 2, 3, or 4 groups independentlyselected from halogen, C₁-C₄ alkoxy, hydroxy, —NO₂, and

[0370] C₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituentsindependently selected from halogen, OH, SH, NH₂, NH(C₁-C₆ alkyl),N-(C₁-C₆ alkyl)(C₁-C₆ alkyl), C≡N, CF₃.

[0371] Preferred compounds of formula I-1 further include those wherein

[0372] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the phenyl or pyridinylrings are each optionally substituted with 1 or 2 groups independentlyselected from halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, hydroxy, —CF₃, and—NO₂.

[0373] Preferred compounds of formula I-1 include those wherein

[0374] R₁ is —CH₂-phenyl where the phenyl ring is optionally substitutedwith 2 groups independently selected from halogen, C₁-C₂ alkyl, C₁-C₂alkoxy, hydroxy, and —NO₂.

[0375] Preferred compounds of formula I-1 also include those wherein R₁is benzyl, or 3,5-difluorobenzyl.

[0376] Preferred compounds of formula I and I-1 include those of formulaI-2, i.e., compounds of formula I or I-1 wherein

[0377] R₂ and R₃ are independently selected from H or C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃alkoxy, and —NR_(1-a)R_(1-b).

[0378] Preferred compounds of formula I-2 include those wherein

[0379] R_(C) is selected from the group consisting of C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂ (C₁-C₆alkyl), —SH, —NR₂₃₅C═ONR₂₃₅R₂₄₀, —C═ONR₂₃₅R₂₄₀, and —S(═O)₂NR₂₃₅R₂₄₀;—(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl is optionallysubstituted with 1, 2, or 3 groups independently selected from the groupconsisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl; —(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl; —[C(R₂₅₅)(R₂₆₀)]₁₋₃—CO—N—(R₂₅₅)₂; —CH(aryl)₂; —CH(heteroaryl)₂;—CH(heterocycloalkyl)₂; —CH(aryl) (heteroaryl); —CO—NR₂₃₅R₂₄₀;—(CH₂)₀₋₁—CH((CH₂)₀₋₆—OH)—(CH₂) O₁-aryl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(-aryl or-heteroaryl)-CO—O(C₁-C₄ alkyl); —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂; (C₁-C₆alkyl)-O—(C₁-C₆ alkyl)-OH; —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂; —H; and—(CH₂)₀₋₆—C(═NR₂₃₅) (NR₂₃₅R₂₄₀); wherein

[0380] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0381] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0382] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0383] R₂₀₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; OH; —NO₂; halogen; —CO₂H; CON; —(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅;—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅; and —(CH₂)₀₋₄—O—(C₁-C₆alkyl optionally substituted with 1, 2, 3, or 5-F);

[0384] wherein each aryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀ orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0385] wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 groups that are independentlyR₂₁₀;

[0386] wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀, orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0387] R₂₀₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF₃,C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), and N-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0388] R₂₁₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N;C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and═O; wherein

[0389] R₂₁₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, —(CH₂)₀₋₂—(aryl), C₃-C₇ cycloalkyl, and—(CH₂)₀₋₂-(heteroaryl), —(CH₂)₀₋₂-(heterocycloalkyl); wherein the arylgroup at each occurrence is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅ or R₂₁₀; wherein the heterocycloalkylgroup at each occurrence is optionally substituted with 1, 2, or 3 R₂₁₀;wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₁₀;

[0390] R₂₂₀ and R₂₂₅ at each occurrence are independently selected fromthe group consisting of —H, —C₁-C₆ alkyl, hydroxy C₁-C₆ alkyl, aminoC₁-C₆ alkyl; halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, —(C₁-C₆alkyl)-O—(C₁-C₃ alkyl), -aryl, -heteroaryl, and -heterocycloalkyl;wherein the aryl group at each occurrence is optionally substituted with1, 2, or 3 R₂₇₀ groups, each heteroaryl is optionally substituted with1, 2, 3, or 4 R₂₀₀, each heterocycloalkyl is optionally substituted with1, 2, 3, or 4 R₂₁₀ wherein

[0391] R₂₇₀ at each occurrence is independently R₂₀₅, C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆alkoxy; C₁-C₆ haloalkoxy; NR₂₃₅R₂₄₀; OH; C≡N; —CO—(C₁-C₄ alkyl); and ═O;wherein the heterocycloalkyl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; wherein each heteroaryl groupat each occurrence is optionally substituted with 1, 2, or 3 R₂₀₅groups;

[0392] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0393] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromthe group consisting of H, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, or

[0394] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms,wherein the carbocycle is optionally substituted with 1 or 2 groups thatare independently OH, methyl, Cl, F, OCH₃, CF₃, NO₂, or CN;

[0395] R₂₅₅ and R₂₆₀ at each occurrence are independently selected fromthe group consisting of H; C₁-C₆ alkyl optionally substituted with 1, 2,or 3 R₂₀₅ groups; —(CH₂)₀₋₄—C₃-C₇ cycloalkyl optionally substituted with1, 2, or 3 R₂₀₅ groups; —(C₁-C₄ alkyl)-aryl; —(C₁-C₄ alkyl)-heteroaryl;—(C₁-C₄ alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-aryl; —(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heteroaryl; and;—(CH₂)₁₋₄—R₂₆₅—(CH₂)_(0-—) ₄-heterocycloalkyl; wherein

[0396] R₂₆₅ at each occurrence is independently —O—, —S— or —N(C₁-C₆alkyl)-;

[0397] each aryl or phenyl is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅, R₂₁₀, or C₁-C₆ alkyl substitutedwith 1, 2, or 3 groups that are independently R₂₀₅ or R₂₁₀.

[0398] Preferred compounds of formula I-2 include those wherein:

[0399] R_(C) is —(CR₂₄₅R₂₅₀)₀₋₄-aryl, or —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl,wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3R₂₀₀ groups.

[0400] Preferred compounds of formula I-2 also include compounds wherein

[0401] R_(C) is —(CR₂₄₅R₂₅₀)-aryl, or —(CR₂₄₅R₂₅₀)-heteroaryl whereineach aryl and heteroaryl is optionally substituted with 1, 2, or 3 R₂₀₀groups.

[0402] Preferred compounds of formula I-2 also include compounds wherein

[0403] R_(C) is —(CH₂)-aryl, or —(CH₂)-heteroaryl, wherein

[0404] each aryl and heteroaryl is optionally substituted with 1, 2, or3 groups selected from OH, —NO₂, halogen, —CO₂H, C—N,—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), and—(CH₂)₀₋₄—SO₂—NR₂₂₀R₂₂₅.

[0405] Preferred compounds of formula I-2 also include compounds wherein

[0406] R_(C) is —(CH₂)-aryl, wherein aryl is optionally substituted with1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C—N.

[0407] Preferred compounds of formula I-2 also include compounds wherein

[0408] R_(C) is —(CH₂)-phenyl, wherein phenyl is optionally substitutedwith 1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C≡N.

[0409] Preferred compounds of formula I-2 also include compounds whereinR_(C) is benzyl.

[0410] Other preferred compounds of formulas I, I-1 and I-2 includecompounds of formula I-3, i.e., those of formulas I, I-1 or I-2 wherein

[0411] R_(N) is:

[0412] wherein

[0413] R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or—NR₅₀CO₂R₅₁;

[0414] wherein

[0415] n₆ is 0, 1, 2, or 3;

[0416] n₇ is 0, 1, 2, or 3;

[0417] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0418] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0419] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0420] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; and cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0421] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0422] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0423] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl;

[0424] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy.

[0425] Preferred compounds of formula I-3 include compounds wherein

[0426] R_(N) is

[0427] wherein

[0428] X is C₁-C₄ alkylidenyl optionally substituted with 1, 2, or 3methyl groups; or —NR₄₋₆—; or

[0429] R₄ and R₄₋₆ combine to form —(CH₂)_(n10)—, wherein

[0430] n₁₀ is 1, 2, 3, or 4;

[0431] Z is selected from a bond; SO₂; SO; S; and C(O);

[0432] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from halogen, hydroxy, alkoxy, thioalkoxy,and haloalkoxy; C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3groups independently selected from C₁-C₃ alkyl, and halogen; alkoxy;phenyl optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy,CN or NO₂; phenyl C₁-C₄ alkyl optionally substituted with halogen, C₁-C₄alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0433] Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; and C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0434] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₃ alkoxy C₁-C₆ alkyl, or halogen.

[0435] Preferred compounds of formula I-3 include compounds wherein

[0436] X is C₁-C₄ alkylidenyl optionally optionally substituted with 1,2, or 3 methyl groups;

[0437] Z is selected from SO₂; SO; S; and C(O);

[0438] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from the group consisting of halogen,hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C₃-C₈ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from C₁-C₃alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen,C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; phenyl C₁-C₄ alkyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0439] Y₁ and Y2 are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0440] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0441] Preferred compounds of formula I-3 include compounds whereinR_(N) is

[0442] and wherein R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅;or —NR₅₀CO₂R₅₁ wherein

[0443] n₆ is 0, 1, 2, or 3;

[0444] n₇ is 0, 1, 2, or 3;

[0445] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0446] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0447] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0448] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0449] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0450] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0451] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl; and

[0452] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy; and

[0453] Y is C₁-C₁₀ alkyl optionally substituted with 1 thru 3substituents which can be the same or different and are selected fromhalogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy.

[0454] Preferred compounds of formula I-3 further include compoundswherein

[0455] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from the group consisting of R₂₀₅,—OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂ (C₁-C₆ alkyl), —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋3—(C₃-C₈) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅-CO₂H, and —CO₂—(C₁-C₄ alkyl);—(CR₂₄₅R₂₅₀)₀₋₄-phenyl; —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl;—(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂;(C₁-C₆ alkyl)-O—(C₁-C₆ alkyl)-OH; or —(CH₂)₀₋₆—C(═NR₂₃₅)(NR₂₃₅R₂₄₀);wherein

[0456] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0457] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0458] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0459] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;or —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0460] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), orN-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0461] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆ alkoxy; C₁-C₆haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N; C₃-C₇ cycloalkyl optionally substitutedwith 1, 2, or 3 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀;—CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0462] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂-(phenyl), C₃-C₇ cycloalkyl, and —(CH₂)₀₋₂-(heteroaryl),—(CH₂)₀₋₂-(heterocycloalkyl); wherein the phenyl group at eachoccurrence is optionally substituted with 1, 2, or 3 groups that areindependently R₂₀₅ or R₂₁₀; wherein the heterocycloalkyl group at eachoccurrence is optionally substituted with 1, 2, or 3 R₂₁₀; wherein eachheteroaryl group at each occurrence is optionally substituted with 1, 2,or 3 R₂₁₀;

[0463] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₆alkyl, hydroxy C₁-C₆ alkyl, halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, and—(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl);

[0464] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0465] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0466] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms.

[0467] Preferred compounds of formula I-3 include compounds wherein

[0468] R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4groups independently selected from halogen, C₁-C₄ alkoxy, hydroxy, andC₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituents halogen,OH, SH, NH₂, NH(C₁-C₆ alkyl), N-(C₁-C₆ alkyl)(C₁-C₆ alkyl), C—N, CF₃;

[0469] R₂ and R₃ are independently selected from H or C₁-C₄ alkyloptionally substituted with 1 substituent selected from halogen, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, NH₂, NH(C₁-C₆ alkyl), and NH(C₁-C₆alkyl)(C₁-C₆ alkyl);

[0470] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from R₂₀₅, —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃ (C₃-C₆) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-phenyloptionally substituted with 1, 2, or 3 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyridazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrimidinyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-furyl;—(CR₂₄₅R₂₅₀)₀₋₃-indolyl; —(CR₂₄₅R₂₅₀)₀₋₃-thienyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrrolyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrazolyl;(CR₂₄₅R₂₅₀)₀₋₃-benzoxazolyl; —(CR₂₄₅R₂₅₀)₀₋₃-imidazolyl; each of theabove heteroaryl groups is optionally substituted with 1, 2, 3, or 4R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-imidazolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-tetrahydrofuryl;(CR₂₄₅R₂₅₀)₀₋₃-tetrahydropyranyl; (CR₂₄₅R₂₅₀)₀₋₃-piperazinyl;(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-piperidinyl;(CR₂₄₅R₂₅₀)₀₋₃-indolinyl; each of the above heterocycloalkyl groups isoptionally substituted with 1, 2, 3, or 4 R₂₁₀;(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl; —(CH₂)₀₋₁—CH(C₁-C₄hydroxyalkyl)-(CH₂)₀₋₁ pyridyl;

[0471] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₈ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;and —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0472] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), andN—(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0473] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1 or 2 R₂₀₅ groups; halogen; C₁-C₄ alkoxy; C₁-C₄haloalkoxy; —NR₂₂₀R₂₂₅; OH; CN; C₃-C₇ cycloalkyl optionally substitutedwith 1 or 2 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀;—SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0474] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂—(phenyl), C₃-C₆ cycloalkyl, —(CH₂)₀₋₂-(pyridyl),—(CH₂)₀₋₂-(pyrrolyl), —(CH₂)₀₋₂-(imidazolyl), —(CH₂)₀₋₂-(pyrimidyl),—(CH₂)₀₋₂-(pyrrolidinyl), —(CH₂)₀₋₂-(imidazolidinyl)—(CH₂)₀₋₂—(piperazinyl), —(CH₂)₀₋₂—(piperidinyl), and—(CH₂)₀₋₂-(morpholinyl); wherein the phenyl group at each occurrence isoptionally substituted with 1 or 2 groups that are independently R₂₀₅ orR₂₁₀; wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1 or 2 R₂₁₀; wherein each heteroaryl groupat each occurrence is optionally substituted with 1 or 2 R₂₁₀;

[0475] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₄alkyl, hydroxy C₁-C₄ alkyl, halo C₁-C₄ alkyl; —C₃-C₆ cycloalkyl, and—(C₁-C₄ alkyl)-O—(C₁-C₂ alkyl)

[0476] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0477] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0478] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, or 6 carbon atoms.

[0479] Other preferred compounds of formula I-3 include compoundswherein

[0480] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1or 2 methyl groups;

[0481] Z is SO₂; SO; S; or C(O);

[0482] Y is C₁-C₄ haloalkyl; OH; —N(Y₁)(Y₂); C₁-C₁₀alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, C₁-C₄ alkoxy, C₁-C₄ thioalkoxy,and C₁-C₄ haloalkoxy; C₁-C₄ alkoxy; phenyl optionally substituted withhalogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; and benzyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0483] Y₁ and Y₂ are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected fromhalogen, C₁-C₂ alkoxy, C₃-C₆ cycloalkyl, and OH; C₂-C₆ alkanoyl; phenyl;—SO₂—C₁-C₄ alkyl; benzyl; and C₃-C₆ cycloalkyl C₁-C₂ alkyl; or

[0484] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0485] Preferred compounds of formula I-3 also include those of formulaI-4, i.e., compounds of formula I-3 wherein

[0486] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1methyl group;

[0487] Z is SO₂; SO; S; or C(O);

[0488] Y is OH; —N(Y₁)(Y₂); phenyl; benzyl; or C₁-C₁₀ alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy,thioethoxy, and CF₃; wherein

[0489] Y₁ and Y₂ are the same or different and are H; C₁-C₄ alkyloptionally substituted with 1 or 2 substituents selected from halogen,methoxy, ethoxy, cyclopropyl, and OH; or

[0490] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄alkoxy, or halogen;

[0491] R₁ is benzyl which is optionally substituted with 1, 2, or 3groups independently selected from methyl, ethyl, n-propyl, isopropyl,hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, —CH₂CF₃,methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, andOH;

[0492] R₂ and R₃ are independently H or C₁-C₄ alkyl;

[0493] R_(C) is C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl,cyclohexyl, cyclohexylmethyl; —(CR₂₄₅R₂₅₀)₀₋₃-phenyl optionallysubstituted with 1 or 2 R₂₀₀ groups; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl optionallysubstituted with 1 or 2 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-piperazinyl; or(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; —(CR₂₄₅R₂₅₀)₀₋₃-piperidinyl; each of theabove heterocycloalkyl groups is optionally substituted with 1 or 2 R₂₁₀groups;

[0494] R₂₀₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; OH; and halogen;

[0495] R₂₀₅ at each occurrence is independently selected from C₁-C₄alkyl, halogen, —OH, —SH, C≡N, —CF₃, and C₁-C₄ alkoxy;

[0496] R₂₁₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; halogen; C₁-C₄alkoxy; OCF₃; NH₂, NH(C₁-C₆ alkyl); N(C₁-C₆ alkyl)(C₁-C₆ alkyl); OH; and—CO—(C₁-C₄ alkyl); wherein

[0497] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromH, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, or

[0498] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 5, or 6 carbon atoms.

[0499] Preferred compounds of formulas I, I-1 and I-2 include compoundsof formula I-5, i.e., those of formulae I, I-1 or I-2 wherein

[0500] R_(N) is —C(═O)—(CRR′)₀₋₆R₁₀₀; and

[0501] R₁₀₀ represents aryl, heteroaryl, or heterocyclyl, where the ringportions of each are optionally substituted with 1, 2, or 3 groupsindependently selected from

[0502] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR′), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀O₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₀₅′—COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0503] Preferred compounds of formula I-5 include compounds wherein

[0504] R_(N) is —C(═O)—R₁₀₀; and

[0505] R₁₀₀ represents aryl, or heteroaryl, where the ring portions ofeach are optionally substituted with 1, 2, or 3 groups independentlyselected from —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R′₁₀₂, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl),—(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₅₀-—COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0506] Preferred compounds of formula I-5 also include compounds wherein

[0507] R_(N) is —C(═O)-aryl or —C(═O)-heteroaryl where the ring portionsof each are optionally substituted with 1, 2, or 3 groups independentlyselected from

[0508] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀O₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′,—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl), —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀,—(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀, —(CH₂)₀₋₄—CO—R₁₃₀,—(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅o,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0509] Other preferred compounds of formula I-5 include compoundswherein

[0510] R_(N) is —C(═O)-aryl or —C(═O)-heteroaryl where the ring portionsof each are optionally substituted with 1 or 2 groups independentlyselected from

[0511] C₁-C₆ alkyl, halogen, —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl, (C₂-C₁₀) alkenyl,—(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀) alkynyl.

[0512] Other preferred compounds of formula I-5 also include compoundswherein R_(N) is:

[0513] wherein sub is hydrogen or is C₁-C₆ alkyl, halogen,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅ C₃-C₇ cycloalkyl,—(C₂-C₁₀)alkenyl, —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or(C₂-C₁₀)alkynyl.

[0514] A preferred stereochemistry for compounds of formula I is asfollows:

[0515] Preferred compounds of formula X include those of formula X-1,i.e., compounds of formula X wherein

[0516] R₁ is aryl, heteroaryl, heterocyclyl, —C₁-C₆ alkyl-aryl, —C₁-C₆alkyl-heteroaryl, or —C₁-C₆ alkyl-heterocyclyl, where the ring portionsof each are optionally substituted with 1, 2, 3, or 4 groupsindependently selected from halogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅,—CO₂R, —N(R)COR′, or —N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino,—SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino,—SO₂—(C₁-C₄) alkyl, or

[0517] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0518] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0519] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0520] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0521] Preferred compounds of formula X-1 also include those wherein

[0522] R₁ is —C₁-C₆ alkyl-aryl, —C₁-C₆ alkyl-heteroaryl, or —C₁-C₆alkyl-heterocyclyl, where the ring portions of each are optionallysubstituted with 1, 2, 3, or 4 groups independently selected fromhalogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or—N(R)SO₂R, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono or dialkylamino,—C(═O)-amino, —C(═O)-mono or dialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0523] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0524] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0525] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0526] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0527] Preferred compounds of formula X-1 further include those wherein

[0528] R₁ is —(CH₂)-aryl, —(CH₂)-heteroaryl, or —(CH₂)-heterocyclyl,where the ring portions of each are optionally substituted with 1, 2, 3,or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO₂,—NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or —N(R)SO₂R, —C(═O)—(C₁-C₄)alkyl,—SO₂-amino, —SO₂-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono ordialkylamino, —SO₂—(C₁-C₄) alkyl, or

[0529] C₁-C₆ alkoxy optionally substituted with 1, 2, or 3 groups whichare independently selected from halogen, or

[0530] C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, —C₁-C₆ alkyl and mono- or dialkylamino, or

[0531] C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groupsindependently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or

[0532] C₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- ordialkylamino; and the heterocyclyl group is optionally furthersubstituted with oxo.

[0533] Preferred compounds of formula X-1 also include those wherein

[0534] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the ring portions ofeach are optionally substituted with 1, 2, 3, or 4 groups independentlyselected from halogen, C₁-C₄ alkoxy, hydroxy, —NO₂, and

[0535] C₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituentsindependently selected from halogen, OH, SH, NH₂, NH(C₁-C₆ alkyl),N-(C₁-C₆ alkyl)(C₁-C₆ alkyl), C≡N, CF₃.

[0536] Preferred compounds of formula X-1 further include those wherein

[0537] R₁ is —CH₂-phenyl or —CH₂-pyridinyl where the phenyl or pyridinylrings are each optionally substituted with 1 or 2 groups independentlyselected from halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, hydroxy, —CF₃, and—NO₂.

[0538] Preferred compounds of formula X-1 include those wherein

[0539] R₁ is —CH₂-phenyl where the phenyl ring is optionally substitutedwith 2 groups independently selected from halogen, C₁-C₂ alkyl, C₁-C₂alkoxy, hydroxy, and —NO₂.

[0540] Preferred compounds of formula X-1 also include those wherein R₁is benzyl, or 3,5-difluorobenzyl.

[0541] Preferred compounds of formula X or X-1 include those of formulaX-2, i.e., compounds of formula X or X-1 wherein

[0542] R₂ and R₃ are independently selected from H or C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃alkoxy, and —NR_(1-a)R_(1-b).

[0543] Preferred compounds of formula X-2 include those wherein

[0544] R_(C) is selected from the group consisting of C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —OC═ONR₂₃₅R₂₄₀, —S(═O)O₂(C₁-C₆alkyl), —SH, —NR₂₃₅C═ONR₂₃₅R₂₄₀—C═ONR₂₃₅R₂₄₀, and —S(═O)₂NR₂₃₅R₂₄₀;—(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl is optionallysubstituted with 1, 2, or 3 groups independently selected from the groupconsisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl; —(CR₂₄₅R₂₅₀)₀₋₄heterocycloalkyl; —[C(R₂₅₅)(R₂₆₀)]₁₋₃—CO—N—(R₂₅₅)₂; —CH(aryl)₂; —CH(heteroaryl)₂;—CH(heterocycloalkyl)₂; —CH(aryl) (heteroaryl); —CO—NR₂₃₅R₂₄₀;—(CH₂)₀₋₁—CH((CH₂)₀₆—OH)—(CH₂)₀₋₁-aryl; —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁heteroaryl; —CH(-aryl or -heteroaryl)-CO—O(C₁-C₄ alkyl);—CH(—CH₂—OH)—CH(OH)-phenyl-NO₂; (C₁-C₆ alkyl)-O—(C₁-C₆ alkyl)-OH;—CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂; —H; and —(CH₂)₀₋₆—C(═NR₂₃₅) (NR₂₃₅R₂₄₀);wherein

[0545] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0546] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0547] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0548] R₂₀₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; OH; —NO₂; halogen; —CO₂H; C≡N; —(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅;—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅; and —(CH₂)_(0-—)₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or 5-F);

[0549] wherein each aryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀ orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0550] wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 groups that are independentlyR₂₁₀;

[0551] wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀, orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀;

[0552] R₂₀₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF₃,C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), and N-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0553] R₂₁₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N;C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—CO—(C₁-C₄ alkyl); SO₂—NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and═O; wherein

[0554] R₂₁₅ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl, —(CH₂)₀₋₂-(aryl), C₃-C₇ cycloalkyl, and—(CH₂)₀₋₂-(heteroaryl), —(CH₂)₀₋₂-(heterocycloalkyl); wherein the arylgroup at each occurrence is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅ or R₂₁₀; wherein the heterocycloalkylgroup at each occurrence is optionally substituted with 1, 2, or 3 R₂₁₀;wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₁₀;

[0555] R₂₂₀ and R₂₂₅ at each occurrence are independently selected fromthe group consisting of —H, —C₁-C₆ alkyl, hydroxy C₁-C₆ alkyl, aminoC₁-C₆ alkyl; halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, —(C₁-C₆alkyl)-O—(C₁-C₃ alkyl), -aryl, -heteroaryl, and -heterocycloalkyl;wherein the aryl group at each occurrence is optionally substituted with1, 2, or 3 R₂₇₀ groups, each heteroaryl is optionally substituted with1, 2, 3, or 4 R₂₀₀, each heterocycloalkyl is optionally substituted with1, 2, 3, or 4 R₂₁₀ wherein

[0556] R₂₇₀ at each occurrence is independently R₂₀₅, C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆alkoxy; C₁-C₆ haloalkoxy; NR₂₃₅R₂₄₀; OH; C≡N; —CO—(C₁-C₄ alkyl); and ═O;wherein the heterocycloalkyl group at each occurrence is optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; wherein each heteroaryl groupat each occurrence is optionally substituted with 1, 2, or 3 R₂₀₅groups;

[0557] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0558] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromthe group consisting of H, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, or

[0559] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms,wherein the carbocycle is optionally substituted with 1 or 2 groups thatare independently OH, methyl, Cl, F, OCH₃, CF₃, NO₂, or CN;

[0560] R₂₅₅ and R₂₆₀ at each occurrence are independently selected fromthe group consisting of H; C₁-C₆ alkyl optionally substituted with 1, 2,or 3 R₂₀₅ groups; —(CH₂)₀₋₄—C₃-C₇ cycloalkyl optionally substituted with1, 2, or 3 R₂₀₅ groups; —(C₁-C₄ alkyl)-aryl; —(C₁-C₄ alkyl)-heteroaryl;—(C₁-C₄ alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl;(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-aryl; —(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heteroaryl; and;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heterocycloalkyl; wherein

[0561] R₂₆₅ at each occurrence is independently —O—, —S— or —N(C₁-C₆alkyl)-;

[0562] each aryl or phenyl is optionally substituted with 1, 2, or 3groups that are independently R₂₀₅, R₂₁₀, or C₁-C₆ alkyl substitutedwith 1, 2, or 3 groups that are independently R₂₀₅ or R₂₁₀.

[0563] Preferred compounds of formula X-2 include those wherein:

[0564] R_(C) is —(CR₂₄₅R₂₅₀)₀₋₄-aryl, or —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl,wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3R₂₀₀ groups.

[0565] Preferred compounds of formula X-2 also include compounds wherein

[0566] R_(C) is —(CR₂₄₅R₂₅₀)-aryl, or —(CR₂₄₅R₂₅₀)-heteroaryl whereineach aryl and heteroaryl is optionally substituted with 1, 2, or 3 R₂₀₀groups.

[0567] Preferred compounds of formula X-2 also include compounds wherein

[0568] R_(C) is —(CH₂)-aryl, or —(CH₂)-heteroaryl, wherein

[0569] each aryl and heteroaryl is optionally substituted with 1, 2, or3 groups selected from OH, —NO₂, halogen, —CO₂H, C≡N,—(CH₂)₀₋₄—CO—NR₂₂OR₂₂₅, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), and—(CH₂)₀₋₄—SO₂—NR₂₂OR₂₂₅.

[0570] Preferred compounds of formula X-2 also include compounds wherein

[0571] R_(C) is —(CH₂)-aryl, wherein aryl is optionally substituted with1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C—N.

[0572] Preferred compounds of formula X-2 also include compounds wherein

[0573] R_(C) is —(CH₂)-phenyl, wherein phenyl is optionally substitutedwith 1, 2, or 3 groups selected from OH, —NO₂, halogen, —CO₂H, and C—N.

[0574] Preferred compounds of formula X-2 also include compounds whereinR_(C) is benzyl.

[0575] Other preferred compounds of formulas X, X-1 or X-2 includecompounds of formula X-3, i.e., those of formulas X, X-1 or X-2 wherein

[0576] R_(N) is:

[0577] wherein

[0578] R₄ is NH₂; —NH—(CH₂),₆—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or —NR₅₀CO₂R₅₁;

[0579] wherein

[0580] n₆ is 0, 1, 2, or 3;

[0581] n₇ is 0, 1, 2, or 3;

[0582] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈-alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0583] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0584] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0585] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0586] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0587] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0588] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl;

[0589] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy.

[0590] Preferred compounds of formula X-3 include compounds wherein

[0591] R_(N) is

[0592] wherein

[0593] X is C₁-C₄ alkylidenyl optionally substituted with 1, 2, or 3methyl groups; or —NR₄₋₆—; or

[0594] R₄ and R₄₋₆ combine to form —(CH₂)_(n10)—, wherein

[0595] n₁₀ is 1, 2, 3, or 4;

[0596] Z is selected from a bond; SO₂; SO; S; and C(O);

[0597] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from halogen, hydroxy, alkoxy, thioalkoxy,and haloalkoxy; C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3groups independently selected from C₁-C₃ alkyl, and halogen; alkoxy;phenyl optionally substituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy,CN or NO₂; phenyl C₁-C₄ alkyl optionally substituted with halogen, C₁-C₄alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0598] Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; and C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0599] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0600] Preferred compounds of formula X-3 include compounds wherein

[0601] X is C₁-C₄ alkylidenyl optionally substituted with 1, 2, or 3methyl groups;

[0602] Z is selected from SO₂; SO; S; and C(O);

[0603] Y is selected from H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkylcontaining at least one N, O, or S; phenyl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyloptionally substituted with 1 thru 3 substituents which can be the sameor different and are selected from the group consisting of halogen,hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C₃-C₈ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from C₁-C₃alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen,C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; phenyl C₁-C₄ alkyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0604] Y₁ and Y₂ are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or

[0605] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0606] Preferred compounds of formula X-3 include compounds whereinR_(N) is

[0607] and wherein R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅;or —NR₅₀CO₂R₅₁ wherein

[0608] n₆ is 0, 1, 2, or 3;

[0609] n₇ is 0, 1, 2, or 3;

[0610] R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄;

[0611] R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, or C₃-C₆cycloalkyl;

[0612] R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, or phenylalkanoyl;

[0613] R₅ is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl;wherein each cycloalkyl group is optionally substituted with one or twogroups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl, C₁-C₆ alkoxy,more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or the cycloalkyl group issubstituted with 1 or 2 groups that are independently CF₃, Cl, F,methyl, ethyl or cyano; C₁-C₆ alkyl optionally substituted with 1, 2, or3 groups that are independently halogen, —NR₆R₇, C₁-C₄ alkoxy, C₅-C₆heterocycloalkyl, C₅-C₆ heteroaryl, phenyl, C₃-C₇ cycloalkyl, —S—C₁-C₄alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, orphenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl,or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groupsthat are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups thatare independently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein

[0614] R₆ and R₇ are independently selected from the group consisting ofH, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenylC₁-C₄ alkyl;

[0615] R₈ is selected from the group consisting of —SO₂-heteroaryloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl or halogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉,heterocycloalkyl, —S—C₂-C₄ alkanoyl, wherein

[0616] R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H or C₁-C₆alkyl; and

[0617] R₅₁ is selected from the group consisting of phenyl C₁-C₄ alkyl;C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups that areindependently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇ or —C₁-C₄alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups thatare independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl,phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; heterocycloalkylalkyloptionally substituted with 1 or 2 groups that are independently C₁-C₄alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenyl C₁-C₄ alkyl, and—SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryl optionally substitutedwith 1, 2, or 3 groups that are independently OH, C₁-C₄ alkyl, C₁-C₄alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl);heteroarylalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl)or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl, andcycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy; and

[0618] Y is C₁-C₁₀ alkyl optionally substituted with 1 thru 3substituents which can be the same or different and are selected fromhalogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy.

[0619] Preferred compounds of formula X-3 further include compoundswherein

[0620] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from the group consisting of R₂₀₅,—OC═ONR₂₃₅R₂₄₀, —S(═O)₀₋₂(C₁-C₆ alkyl), —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl);—(CR₂₄₅R₂₅₀)₀₋₄-phenyl; —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄heterocycloalkyl;—(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂;(C₁-C₆ alkyl)-O—(C₁-C₆ alkyl)-OH; or —(CH₂)₀₋₆—C(═NR₂₃₅)(NR₂₃₅R₂₄₀);wherein

[0621] each aryl is optionally substituted with 1, 2, or 3 R₂₀₀;

[0622] each heteroaryl is optionally substituted with 1, 2, 3, or 4R₂₀₀;

[0623] each heterocycloalkyl is optionally substituted with 1, 2, 3, or4 R₂₁₀;

[0624] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;or —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0625] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), orN-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0626] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆ alkoxy; C₁-C₆haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N; C₃-C₇ cycloalkyl optionally substitutedwith 1, 2, or 3 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀;—CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0627] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂-(phenyl), C₃-C₇ cycloalkyl, and —(CH₂)₀₋₂-(heteroaryl),—(CH₂)₀₋₂-(heterocycloalkyl); wherein the phenyl group at eachoccurrence is optionally substituted with 1, 2, or 3 groups that areindependently R₂₀₅ or R₂₁₀; wherein the heterocycloalkyl group at eachoccurrence is optionally substituted with 1, 2, or 3 R₂₁₀; wherein eachheteroaryl group at each occurrence is optionally substituted with 1, 2,or 3 R₂₁₀;

[0628] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₆alkyl, hydroxy C₁-C₆ alkyl, halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, and—(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl);

[0629] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0630] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0631] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms.

[0632] Preferred compounds of formula X-3 include compounds wherein

[0633] R₁ is benzyl which is optionally substituted with 1, 2, 3, or 4groups independently selected from halogen, C₁-C₄ alkoxy, hydroxy, andC₁-C₄ alkyl optionally substituted with 1, 2, or 3 substituents halogen,OH, SH, NH₂, NH(C₁-C₆ alkyl), N-(C₁-C₆ alkyl)(C₁-C₆ alkyl), C≡N, CF₃;

[0634] R₂ and R₃ are independently selected from H or C₁-C₄ alkyloptionally substituted with 1 substituent selected from halogen, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, NH₂, NH(C₁-C₆ alkyl), and NH(C₁-C₆alkyl)(C₁-C₆ alkyl);

[0635] R_(C) is C₁-C₈ alkyl optionally substituted with 1, 2, or 3groups independently selected from R₂₀₅, —SH, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃—(C₃-C₆) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl); —(CR₂₄₅R₂₅₀)₀₋₄-phenyloptionally substituted with 1, 2, or 3 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyridazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrimidinyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrazinyl; —(CR₂₄₅R₂₅₀)₀₋₃-furyl;—(CR₂₄₅R₂₅₀)₀₋₃-indolyl; —(CR₂₄₅R₂₅₀)₀₋₃-thienyl;—(CR₂₄₅R₂₅₀)₀₋₃-pyrrolyl; —(CR₂₄₅R₂₅₀)₀₋₃-pyrazolyl;(CR₂₄₅R₂₅₀)₀₋₃-benzoxazolyl; —(CR₂₄₅R₂₅₀)₀₋₃-imidazolyl; each of theabove heteroaryl groups is optionally substituted with 1, 2, 3, or 4R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-iimidazolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-tetrahydrofuryl;(CR₂₄₅R₂₅₀)₀₋₃-tetrahydropyranyl; (CR₂₄₅R₂₅₀)₀₋₃-piperazinyl;(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; (CR₂₄₅R₂₅₀)₀₋₃-piperidinyl;(CR₂₄₅R₂₅₀)₀₋₃-indolinyl; each of the above heterocycloalkyl groups isoptionally substituted with 1, 2, 3, or 4 R₂₁₀;(CH₂)₀₋₁—CH((CH₂)₀₋₄—OH)—(CH₂)₀₋₁-phenyl; —(CH₂)₀₋₁—CH(C₁-C₄hydroxyalkyl)-(CH₂)₀₋₁-pyridyl;

[0636] R₂₀₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen; —CO₂H; C≡N;—(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₈ alkyl); —(CH₂)₀₋₄—CO₂R₂₁₅;and —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with 1, 2, 3, or5-F);

[0637] R₂₀₅ at each occurrence is independently C₁-C₆ alkyl, halogen,—OH, —O-phenyl, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, NH₂, NH(C₁-C₆ alkyl), andN-(C₁-C₆ alkyl)(C₁-C₆ alkyl);

[0638] R₂₁₀ at each occurrence is independently C₁-C₆ alkyl optionallysubstituted with 1 or 2 R₂₀₅ groups; halogen; C₁-C₄ alkoxy; C₁-C₄haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N; C₃-C₇ cycloalkyl optionally substitutedwith 1 or 2 R₂₀₅ groups; —CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀;—SO₂—(C₁-C₄ alkyl); and ═O; wherein

[0639] R₂₁₅ at each occurrence is independently C₁-C₆ alkyl,—(CH₂)₀₋₂-(phenyl), C₃-C₆ cycloalkyl, —(CH₂)₀₋₂-(pyridyl),—(CH₂)₀₋₂—(pyrrolyl), —(CH₂)₀₋₂-(imidazolyl), —(CH₂)₀₋₂-(pyrimidyl),—(CH₂)₀₋₂-(pyrrolidinyl), —(CH₂)₀₋₂-(imidazolidinyl)—(CH₂)₀₋₂-(piperazinyl), —(CH₂)₀₋₂-(piperidinyl), and—(CH₂)₀₋₂-(morpholinyl); wherein the phenyl group at each occurrence isoptionally substituted with 1 or 2 groups that are independently R₂₀₅ orR₂₁₀; wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1 or 2 R₂₁₀; wherein each heteroaryl groupat each occurrence is optionally substituted with 1 or 2 R₂₁₀;

[0640] R₂₂₀ and R₂₂₅ at each occurrence are independently —H, —C₁-C₄alkyl, hydroxy C₁-C₄ alkyl, halo C₁-C₄ alkyl; —C₃-C₆ cycloalkyl, and—(C₁-C₄ alkyl)-O—(C₁-C₂ alkyl);

[0641] R₂₃₅ and R₂₄₀ at each occurrence are independently H, or C₁-C₆alkyl;

[0642] R₂₄₅ and R₂₅₀ at each occurrence are independently H, C₁-C₄alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, or

[0643] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 4, 5, or 6 carbon atoms.

[0644] Other preferred compounds of formula X-3 include compoundswherein

[0645] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1or 2 methyl groups;

[0646] Z is SO₂; SO; S; or C(O);

[0647] Y is C₁-C₄ haloalkyl; OH; —N(Y) (Y₂); C₁-C₁₀ alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, C₁-C₄ alkoxy, C₁-C₄ thioalkoxy,and C₁-C₄ haloalkoxy; C₁-C₄ alkoxy; phenyl optionally substituted withhalogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; and benzyl optionallysubstituted with halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, CN or NO₂; wherein

[0648] Y₁ and Y₂ are the same or different and are H; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 substituents selected fromhalogen, C₁-C₂ alkoxy, C₃-C₆ cycloalkyl, and OH; C₂-C₆ alkanoyl; phenyl;—SO₂—C₁-C₄ alkyl; benzyl; and C₃-C₆ cycloalkyl C₁-C₂ alkyl; or

[0649] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1, 2, 3, or 4 groups that are independently C₁-C₆alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, or halogen.

[0650] Preferred compounds of formula X-3 also include those of formulaX-4, i.e., compounds of formula X-3 wherein

[0651] X is —C₁-C₃ alkylidenyl optionally optionally substituted with 1methyl group;

[0652] Z is SO₂; SO; S; or C(O);

[0653] Y is OH; —N(Y₁)(Y₂); phenyl; benzyl; or C₁-C₁₀ alkyl optionallysubstituted with 1 or 2 substituents which can be the same or differentand are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy,thioethoxy, and CF₃; wherein

[0654] Y₁ and Y₂ are the same or different and are H; C₁-C₄ alkyloptionally substituted with 1 or 2 substituents selected from halogen,methoxy, ethoxy, cyclopropyl, and OH; or

[0655] —N(Y₁)(Y₂) forms a ring selected from piperazinyl, piperidinyl,morpholinyl, and pyrolidinyl, wherein each ring is optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄alkoxy, or halogen;

[0656] R₁ is benzyl which is optionally substituted with 1, 2, or 3groups independently selected from methyl, ethyl, n-propyl, isopropyl,hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, —CH₂CF₃,methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, andOH;

[0657] R₂ and R₃ are independently H or C₁-C₄ alkyl;

[0658] R_(C) is C₃-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl,cyclohexyl, cyclohexylmethyl; —(CR₂₄₅R₂₅₀)₀₋₃-phenyl optionallysubstituted with 1 or 2 R₂₀₀ groups; —(CR₂₄₅R₂₅₀)₀₋₃-pyridyl optionallysubstituted with 1 or 2 R₂₀₀; —(CR₂₄₅R₂₅₀)₀₋₃-piperazinyl; or(CR₂₄₅R₂₅₀)₀₋₃-pyrrolidinyl; —(CR₂₄₅R₂₅₀)₀₋₃-piperidinyl; each of theabove heterocycloalkyl groups is optionally substituted with 1 or 2 R₂₁₀groups;

[0659] R₂₀₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; OH; and halogen;

[0660] R₂₀₅ at each occurrence is independently selected from C₁-C₄alkyl, halogen, —OH, —SH, —C≡N, —CF₃, and C₁-C₄ alkoxy;

[0661] R₂₁₀ at each occurrence is independently selected from C₁-C₄alkyl optionally substituted with 1 or 2 R₂₀₅ groups; halogen; C₁-C₄alkoxy; OCF₃; NH₂, NH(C₁-C₆ alkyl); N(C₁-C₆ alkyl)(C₁-C₆ alkyl); OH; and—CO—(C₁-C₄ alkyl); wherein

[0662] R₂₄₅ and R₂₅₀ at each occurrence are independently selected fromH, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, or

[0663] R₂₄₅ and R₂₅₀ are taken together with the carbon to which theyare attached to form a carbocycle of 3, 5, or 6 carbon atoms.

[0664] Preferred compounds of formulas X, X-1 and X-2 include compoundsof formula X-5, i.e., those of formulae X, X-1 or X-2 wherein

[0665] R_(N) is —C(═O)—(CRR′)₀₋₆R₁₀₀; and

[0666] R₁₀₀ represents aryl, heteroaryl, or heterocyclyl, where the ringportions of each are optionally substituted with 1, 2, or 3 groupsindependently selected from

[0667] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄-O—P(═O)(OR)(OR), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)_(0-4-CO—(C) ₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀,—(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀, —(CH₂)₀₋₄—CO—R₁₃₀,—(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅, —(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀,—(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), —(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀),(CH₂)₀₋₄—O—R₁₅₀—COOH, —(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0668] Preferred compounds of formula X-5 include compounds wherein

[0669] R_(N) is —C(═O)—R₁₀₀; and

[0670] R₁₀₀ represents aryl, or heteroaryl, where the ring portions ofeach are optionally substituted with 1, 2, or 3 groups independentlyselected from

[0671] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄ (C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀,—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀,—(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀O₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₁₀, —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂(C₁-C₁₂ alkyl), —(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl),—(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀, —(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—O—R₁₅₀′-COOH,—(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅—(CH₂)₀₋₄—C₃-C₇cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0672] Preferred compounds of formula X-5 also include compounds wherein

[0673] R_(N) is —C(═O)-aryl or —C(═O)-heteroaryl where the ring portionsof each are optionally substituted with 1, 2, or 3 groups independentlyselected from

[0674] —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′—(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—R₁₁₀—(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀,—(CH₂)₀₋₄—CO—R₁₂₀, —(CH₂)₀₋₄—CO—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₄₀,—(CH₂)₀₋₄—CO—O—R₁₅₀, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—SO—(C₁-C₈alkyl), —(CH₂)₀₋₄—SO₂ (C₁-C₁₂ alkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅,—(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀, —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, or (C₂-C₁₀)alkynyl.

[0675] Other preferred compounds of formula X-5 include compoundswherein

[0676] R_(N) is —C(═O)-aryl or —C(═O)-heteroaryl where the ring portionsof each are optionally substituted with 1 or 2 groups independentlyselected from

[0677] C₁-C₆ alkyl, halogen, —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl, (C₂-C₁₀) alkenyl,—(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀) alkynyl.

[0678] Other preferred compounds of formula X-5 also include compoundswherein R_(N) is:

[0679] wherein sub is hydrogen or is C₁-C₆ alkyl, halogen,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂—(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl, —(C₂-C₁₀)alkenyl,—(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀)alkynyl.

[0680] A preferred stereochemistry for compounds of formula X is asfollows:

[0681] In another aspect, the invention provides intermediates of theformula (IA):

[0682] wherein R₁, R₂, R₃, R_(N), and R_(C) are as defined above forcompounds of formula I, and PROT is an amine protecting group as definedbelow.

[0683] In another aspect, the invention provides intermediates of theformula (XA):

[0684] wherein R₁, R₂, R₃, R_(N), and R_(C) are as defined above forcompounds of formula I, and PROT is an amine protecting group as definedbelow

[0685] The invention also provides methods of generating compounds offormula (Y) from the compounds of formula (AA), formula (I) or formula(X), which are useful for treating and/or preventing Alzheimer'sdisease. The generation of compounds of formula (Y) from compounds offormulae (AA), (I) or (X) can occur in vivo or in vitro.

[0686] The invention also provides processes for converting compounds offormula AA, I or X to the compounds of formula Y by exposing compoundsof formula AA, I or X to aqueous media. The conversion can occur invitro or in vivo.

[0687] The invention also provides methods for treating a patient whohas, or in preventing a patient from getting, a disease or conditionselected from the group consisting of Alzheimer's disease, for helpingprevent or delay the onset of Alzheimer's disease, for treating patientswith mild cognitive impairment (MCI) and preventing or delaying theonset of Alzheimer's disease in those who would progress from MCI to AD,for treating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobar hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, or diffuse Lewy body typeof Alzheimer's disease and who is in need of such treatment whichincludes administration of a therapeutically effective amount of acompound of formula (AA), (I) or (X) or a pharmaceutically acceptablesalts thereof.

[0688] In an embodiment, this method of treatment can be used where thedisease is Alzheimer's disease.

[0689] In an embodiment, this method of treatment can help prevent ordelay the onset of Alzheimer's disease.

[0690] In an embodiment, this method of treatment can be used where thedisease is mild cognitive impairment.

[0691] In an embodiment, this method of treatment can be used where thedisease is Down's syndrome.

[0692] In an embodiment, this method of treatment can be used where thedisease is Hereditary Cerebral Hemorrhage with Amyloidosis of theDutch-Type.

[0693] In an embodiment, this method of treatment can be used where thedisease is cerebral amyloid angiopathy.

[0694] In an embodiment, this method of treatment can be used where thedisease is degenerative dementias.

[0695] In an embodiment, this method of treatment can be used where thedisease is diffuse Lewy body type of Alzheimer's disease.

[0696] In an embodiment, this method of treatment can treat an existingdisease.

[0697] In an embodiment, this method of treatment can prevent a diseasefrom developing.

[0698] In an embodiment, this method of treatment can employtherapeutically effective amounts: for oral administration from about0.1 mg/day to about 1,000 mg/day; for parenteral, sublingual,intranasal, intrathecal administration from about 0.5 to about 100mg/day; for depo administration and implants from about 0.5 mg/day toabout 50 mg/day; for topical administration from about 0.5 mg/day toabout 200 mg/day; for rectal administration from about 0.5 mg to about500 mg.

[0699] In an embodiment, this method of treatment can employtherapeutically effective amounts: for oral administration from about 1mg/day to about 100 mg/day; and for parenteral administration from about5 to about 50 mg daily.

[0700] In an embodiment, this method of treatment can employtherapeutically effective amounts for oral administration from about 5mg/day to about 50 mg/day.

[0701] The invention also includes pharmaceutical compositions whichinclude a compound of formula (AA), (I) or (X) or a pharmaceuticallyacceptable salts thereof.

[0702] The invention also includes the use of a compound of formula(AA), (I) or (X) or pharmaceutically acceptable salts thereof for themanufacture of a medicament.

[0703] The invention also includes methods for inhibiting beta-secretaseactivity, for inhibiting cleavage of amyloid precursor protein (APP), ina reaction mixture, at a site between Met596 and Asp597, numbered forthe APP-695 amino acid isotype, or at a corresponding site of an isotypeor mutant thereof; for inhibiting production of amyloid beta peptide (Abeta) in a cell; for inhibiting the production of beta-amyloid plaque inan animal; and for treating or preventing a disease characterized bybeta-amyloid deposits in the brain. These methods each includeadministration of a therapeutically effective amount of a compound offormula (AA), (I) or (X) or a pharmaceutically acceptable salts thereof.

[0704] The invention also includes a method for inhibitingbeta-secretase activity, including exposing said beta-secretase to acompound of formula (AA), (I) or (X), under conditions whereby aneffective inhibitory amount of a compound of formula (Y), or apharmaceutically acceptable salt thereof, is formed.

[0705] In an embodiment, this method employs a compound that inhibits50% of the enzyme's activity at a concentration of less than 50micromolar.

[0706] In an embodiment, this method employs a compound that inhibits50% of the enzyme's activity at a concentration of 10 micromolar orless.

[0707] In an embodiment, this method employs a compound that inhibits50% of the enzyme's activity at a concentration of 1 micromolar or less.

[0708] In an embodiment, this method employs a compound that inhibits50% of the enzyme's activity at a concentration of 10 nanomolar or less.

[0709] In an embodiment, this method includes exposing saidbeta-secretase to said compound in vitro.

[0710] In an embodiment, this method includes exposing saidbeta-secretase to said compound in a cell.

[0711] In an embodiment, this method includes exposing saidbeta-secretase to said compound in a cell in an animal.

[0712] In an embodiment, this method includes exposing saidbeta-secretase to said compound in a human.

[0713] The invention also includes a method for inhibiting cleavage ofamyloid precursor protein (APP), in a reaction mixture, at a sitebetween Met596 and Asp597, numbered for the APP-695 amino acid isotype;or at a corresponding site of an isotype or mutant thereof, includingexposing said reaction mixture to an effective inhibitory amount of acompound of formula (AA), (I) or (X), or a pharmaceutically acceptablesalt thereof. In an embodiment, this method employs a cleavage site:between Met652 and Asp653, numbered for the APP-751 isotype; between Met671 and Asp 672, numbered for the APP-770 isotype; between Leu596 andAsp597 of the APP-695 Swedish Mutation; between Leu652 and Asp653 of theAPP-751 Swedish Mutation; or between Leu671 and Asp672 of the APP-770Swedish Mutation.

[0714] In an embodiment, this method exposes said reaction mixture invitro.

[0715] In an embodiment, this method exposes said reaction mixture in acell.

[0716] In an embodiment, this method exposes said reaction mixture in ananimal cell.

[0717] In an embodiment, this method exposes said reaction mixture in ahuman cell.

[0718] The invention also includes a method for inhibiting production ofamyloid beta peptide (A beta) in a cell, including administering to saidcell a compound of formula (AA), (I) or (X), under conditions whereby aneffective inhibitory amount of a compound of formula (Y), or apharmaceutically acceptable salt thereof, is formed.

[0719] In an embodiment, this method includes administering to ananimal.

[0720] In an embodiment, this method includes administering to a human.

[0721] The invention also includes a method for inhibiting theproduction of beta-amyloid plaque in an animal, including administeringto said animal a compound of formula (AA), (I) or (X), under conditionswhereby an effective inhibitory amount of a compound of formula (Y), ora pharmaceutically acceptable salt thereof, is formed.

[0722] In an embodiment, this method includes administering to a human.

[0723] The invention also includes a method for treating or preventing adisease characterized by beta-amyloid deposits in the brain includingadministering to a patient an effective therapeutic amount of a compoundof formula (AA), (I) or (X), under conditions whereby an effectiveinhibitory amount of a compound of formula (Y), or a pharmaceuticallyacceptable salt thereof, is formed.

[0724] In an embodiment, this method results in a compound of formula(Y) that inhibits 50% of the enzyme's activity at a concentration ofless than 50 micromolar.

[0725] In an embodiment, this method results in a compound of formula(Y) that inhibits 50% of the enzyme's activity at a concentration of 10micromolar or less.

[0726] In an embodiment, this method results in a compound of formula(Y) that inhibits 50% of the enzyme's activity at a concentration of 1micromolar or less.

[0727] In an embodiment, this method results in a compound of formula(Y) that inhibits 50% of the enzyme's activity at a concentration of 10nanomolar or less.

[0728] In an embodiment, this method employs a compound at a therapeuticamount in the range of from about 0.1 to about 1500 mg/day.

[0729] In an embodiment, this method employs a compound at a therapeuticamount in the range of from about 15 to about 1000 mg/day.

[0730] In an embodiment, this method employs a compound at a therapeuticamount in the range of from about 1 to about 100 mg/day.

[0731] In an embodiment, this method employs a compound at a therapeuticamount in the range of from about 5 to about 50 mg/day.

[0732] In an embodiment, this method can be used where said disease isAlzheimer's disease.

[0733] In an embodiment, this method can be used where said disease isMild Cognitive Impairment, Down's Syndrome, or Hereditary CerebralHemorrhage with Amyloidosis of the Dutch Type.

[0734] The invention also includes a component kit including componentparts capable of being assembled, in which at least one component partincludes a compound of formula AA, I or X enclosed in a container.

[0735] In an embodiment, this component kit includes lyophilizedcompound, and at least one further component part includes a diluent.

[0736] The invention also includes a container kit including a pluralityof containers, each container including one or more unit dose of acompound of formula (AA), (I) or (X):, or a pharmaceutically acceptablesalt thereof.

[0737] In an embodiment, this container kit includes each containeradapted for oral delivery and includes a tablet, gel, or capsule.

[0738] In an embodiment, this container kit includes each containeradapted for parenteral delivery and includes a depot product, syringe,ampoule, or vial.

[0739] In an embodiment, this container kit includes each containeradapted for topical delivery and includes a patch, medipad, ointment, orcream.

[0740] The invention also includes an agent kit including a compound offormula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof;and one or more therapeutic agent selected from the group consisting ofan antioxidant, an anti-inflammatory, a gamma secretase inhibitor, aneurotrophic agent, an acetyl cholinesterase inhibitor, a statin, an Abeta peptide, and an anti-A beta antibody.

[0741] The invention also includes a composition including a compound offormula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof;and an inert diluent or edible carrier.

[0742] In an embodiment, this composition includes a carrier that is anoil.

[0743] The invention also includes a composition including: a compoundof formula (AA), (I) or (X), or a pharmaceutically acceptable saltthereof; and a binder, excipient, disintegrating agent, lubricant, orgildant.

[0744] The invention also includes a composition including a compound offormula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof;disposed in a cream, ointment, or patch.

[0745] The invention provides compounds of formula (AA), formula (I) and(X) that can be used to generate compounds of formula (Y), that areuseful in treating and preventing Alzheimer's disease. The compounds ofthe invention can be prepared by one skilled in the art based only onknowledge of the compound's chemical structure. The chemistry for thepreparation of the compounds of this invention is known to those skilledin the art. In fact, there is more than one process to prepare thecompounds of the invention. Specific examples of methods of preparationcan be found in the art. For examples, see J. Org. Chem. 1998, 63,4898-4906; J. Org. Chem. 1997, 62, 9348-9353; J. Org. Chem. 1996, 61,5528-5531; J. Med. Chem. 1993, 36, 320-330; J. Am. Chem. Soc. 1999, 121,1145-1155; and references cited therein. See also U.S. Pat. Nos.6,150,530, 5,892,052, 5,696,270, and 5,362,912, which are incorporatedherein by reference, and references cited therein.

[0746] Examples of various processes that can be used to prepare thecompounds of the invention are set forth below.

[0747] A general process to prepare the compounds of formula I and X isset forth in SCHEME A. The chemistry is straight forward and in summaryinvolves the steps of N-protecting the amino acid (A) starting materialto produce the corresponding protected amino acid (II), reaction of theprotected amino acid (II) with diazomethane followed by work-up to add acarbon atom to produce the corresponding protected compound (III),reduction of the protected halide to the corresponding alcohol (IV),formation of the corresponding epoxide (V), opening of the epoxide (V)with a C-terminal amine, R_(C)—NH₂ (VI) to produce the correspondingprotected alcohol (VII).

[0748] Compounds of formula (I) can be prepared by reacting protectedalcohol (VII) with an amide forming agent such as, for example,(R_(N)—)₂O or R_(N)—X or R_(N)—OH (IX) to produce alcohol (IA). Alcohol(IA) then has the nitrogen protecting group removed to produce thecorresponding compounds of formula (I).

[0749] Compounds of formula (X) can be prepared by further N-protectingalcohol (VII) to form the diprotected alcohol (XB). Diprotected alcohol(XB) is reacted with an amide forming agent such as, for example,(R_(N)—)₂O or R_(N)—X or R_(N)—OH (IX) to produce compound (XA).Compound (XA) then has the nitrogen protecting groups removed to producethe corresponding compounds of formula (X).

[0750] One skilled in the art will appreciate that these are all knownreactions in organic chemistry. A chemist skilled in the art, knowingthe chemical structure of the compounds (AA), (I) and (X) of theinvention would be able to prepare them by known methods from knownstarting materials without any additional information. The explanationbelow therefore is not necessary but is deemed helpful to those skilledin the art who desire to make the compounds of the invention.

[0751] The backbone of the intermediate (VII), from which the compoundsof formula (AA), (I) and (X) can be readily prepared, can be considereda hydroxyethylamine moiety, —NH—CH(R)—CH(OH)—. Such backbones can beprepared by methods disclosed in the literature and known to thoseskilled in the art. For example, J. Med. Chem., 36, 288-291 (1993),Tetrahedron Letters, 28, 5569-5572 (1987), J. Med. Chem., 38, 581-584(1995) and Tetrahedron Letters, 38, 619-620 (1997) and WO 02/02506 alldisclose processes to prepare hydroxyethylamine type compounds and/ortheir intermediates.

[0752] SCHEME A sets forth a general method used in the invention toprepare the appropriately substituted amines I and X. The compounds ofthe invention are prepared by starting with the corresponding amino acid(A). The amino acids (A) are known to those skilled in the art or can bereadily prepared by methods known to those skilled in the art. Thecompounds of the invention have at least two chiral centers, which give2 sets of diastereomers, each of which is racemic for a total of atleast four stereoisomers. While biologically active end products resultfrom all stereoisomers, the (S,R) configuration is preferred. The firstof these chiral centers (the carbon carrying R₁) derives from the aminoacid starting material (A). It is preferred to commercially obtain orproduce the desired enantiomer rather than produce an enantiomericallyimpure mixture and then have to separate out the desired enantiomer.Thus it is preferred to start the process with enantiomerically pure(S)-amino acid (A) of the same configuration as that of the desired Xproduct.

[0753] In Scheme A, the protection of free amine (A) to produce the(S)-protected amino acid (II) is depicted. Amino protecting groups areknown to those skilled in the art, as discussed below. See for example,“Protecting Groups in Organic Synthesis”, John Wiley and sons, New York,N.Y., 1981, Chapter 7; “Protecting Groups in Organic Chemistry”, PlenumPress, New York, N.Y., 1973, Chapter 2. The function of the aminoprotecting group is to protect the free amino functionality (—NH₂)during subsequent reactions on the (S)-amino acid (A) which would notproceed either because the amino group would react and be functionalizedin a way that is inconsistent with its need to be free for subsequentreactions or the free amino group would interfere in the reaction. Whenthe amino protecting group is no longer needed, it is removed by methodsknown to those skilled in the art. By definition the amino protectinggroup must be readily removable as is known to those skilled in the artby methods known to those skilled in the art. Suitable amino PROTECTINGGROUPs are discussed below.

[0754] The (S)-protected amino acid (II) is transformed to thecorresponding (S)-protected compound (III) by two different methodsdepending on nature of R₂ and R₃.

[0755] R₂ and R₃ can be the same or different. It is preferred that R₂and R₃ both be —H. If R₂ and R₃ are not the same, an additional chiralor stereogenic center is added to the molecule. To produce compounds offormula (III) where R₂ and R₃ are both —H, the (S)-protected amino acid(II) is reacted with diazomethane, as is known to those skilled in theart, followed by reaction with a compound of the formula H—X₁ to producethe (S)-protected compound (III). X1 includes —Cl, —Br, —I, —O-tosylate,—O-mesylate, —O-nosylate and —O-brosylate. It is preferred that —X₁ be—Br or —Cl. Suitable reaction conditions include running the reaction ininert solvents, such as but not limited to ether, tetrahydrofuran andthe like. The reactions from the (S)-protected amino acid (II) to the(S)-protected compound (III) are carried out for a period of timebetween 10 minutes and 1 day and at temperatures ranging from about −78°to about 20-25°. It is preferred to conduct the reactions for a periodof time between 1-4 hours and at temperatures between −30° to −10°. Thisprocess adds one methylene group.

[0756] Alternatively, the (S)-protected compounds of formula (III) canbe prepared by first converting the (S)-protected amino acid (II) to acorresponding methyl or ethyl ester, according to methods established inthe art, followed by treatment with a reagent of formula X₁—C(R₂)(R₃)—X₁ and a strong metal base. The base serves to affect ahalogen-metal exchange, where the —X₁ undergoing exchange is a halogenselected from chlorine, bromine or iodine. The nucleophilic addition tothe ester derivative gives directly the (S)-protected compound (III).Suitable bases include, but are not limited to the alkyllithiumsincluding, for example, sec-butyllithium, n-butyllithium, andt-butyllithium. The reactions are preferably conducted at lowtemperature, such as −78°. Suitable reaction conditions include runningthe reaction in inert solvents, such as but not limited to, ether,tetrahydrofuran and the like. Where R₂ and R₃ are both hydrogen, thenexamples of X₁—C(R₂) (R₃)—X₁ include dibromomethane, diiodomethane,chloroiodomethane, bromoiodomethane and bromochloromethane. One skilledin the art knows the preferred conditions required to conduct thisreaction. Furthermore, if R₂ and/or R₃ are not —H, then by the additionof —C(R₂) (R₃)—X₁ to esters of the (S)-protected amino acid (II) toproduce the (S)-protected compound (III), an additional chiral centerwill be incorporated into the product, provided that R₂ and R₃ are notthe same.

[0757] The (S)-protected compound (III) is then reduced by means knownto those skilled in the art for reduction of a ketone to thecorresponding secondary alcohol affording the corresponding alcohol(IV). The means and reaction conditions for reducing the (S)-protectedcompound (III) to the corresponding alcohol (IV) include, for example,sodium borohydride, lithium borohydride, borane, diisobutylaluminumhydride, and lithium aluminium hydride. Sodium borohydride is thepreferred reducing agent. The reductions are carried out for a period oftime between 1 hour and 3 days at temperatures ranging from −78° toelevated temperature up to the reflux point of the solvent employed. Itis preferred to conduct the reduction between −78° and 0°. If borane isused, it may be employed as a complex, for example, borane-methylsulfide complex, borane-piperidine complex, or borane-tetrahydrofurancomplex. The preferred combination of reducing agents and reactionconditions needed are known to those skilled in the art, see forexample, Larock, R. C. in Comprehensive Organic Transformations, VCHPublishers, 1989. The reduction of the (S)-protected compound (III) tothe corresponding alcohol (IV) produces the second chiral center (thirdchiral center if R₂ and R₃ are not the same). The reduction of the(S)-protected compound (III) produces a mixture of enantiomers at thesecond center, (S, R/S)-alcohol (IV). This enantiomeric mixture is thenseparated by means known to those skilled in the art such as selectivelow-temperature recrystallization or chromatographic separation, forexample by HPLC, employing commercially available chiral columns. Theenantiomer that is used in the remainder of the process of SCHEME A isthe (S,S)-alcohol (IV) since this enantiomer will give the desired(S,R)-substituted compound I or X.

[0758] The (S, S)-alcohol (IV) is transformed to the correspondingepoxide (V) by means known to those skilled in the art. Thestereochemistry of the (S)-(IV) center is maintained in forming theepoxide (V). A preferred means is by reaction with base, for example,but not limited to, hydroxide ion generated from sodium hydroxide,potassium hydroxide, lithium hydroxide and the like. Reaction conditionsinclude the use of C₁-C₆ alcohol solvents; ethanol is preferred. Acommon co-solvent, such as for example, ethyl acetate may also beemployed. Reactions are conducted at temperatures ranging from −45° upto the reflux temperature of the alcohol employed; preferred temperatureranges are between −20° and 40°.

[0759] An alternative, and preferable process for preparing the epoxide(V) when R₁ is 3,5-difluorobenzyl, is set forth in SCHEME D. The firststep of the process is to protect the free amino group of the (S)-aminoacid (A) with an amino protecting group, PROTECTING GROUP, as previouslydiscussed to produce the (S)-protected amino acid (II).

[0760] In the alternative process, the (S)-protected amino acid (A) istransformed to the corresponding (S)-protected ester (XVII) in one of anumber of ways. One method involves the use of lithium hydroxide. Usinglithium hydroxide, the (S)-protected amino acid (A) and the lithiumhydroxide are mixed and cooled to from about −20° to about 10°. Next amethylating agent, selected from the group consisting ofdimethylsulfate, methyl iodide and methyl triflate, is added. It is morepreferred that the methylating agent is dimethylsulfate. This isfollowed by heating to from about 20° to about 50°.

[0761] Alternatively, the (S)-protected amino acid (A) is contacted witha weak base such as bicarbonate or preferably carbonate. This isfollowed by addition of the methylating agent. Heat is not necessary butcan be used to facilitate the reaction. The carbonate method is known tothose skilled in the art. For those (S)-protected esters (XVII) where Z,is not methyl, one skilled in the art knowing the chemical structurewould know how to prepare the desired compounds from known startingmaterials. In one known method the (S)-protected amino acid (A) iscontacted with an activating agent, such as DCC, followed by addition ofthe appropriate alcohol, Z₁—OH. This method is operable when Z₁ is C₁-C₄alkyl (optionally substituted), —CH₂—CH═CH₂ or phenyl (optionallysubstituted).

[0762] SCHEME E sets forth an alternative process for the preparation ofthe ester (II). In the process of SCHEME E, the aldehyde (XX), which isknown to those skilled in the art, is reacted with the phosphorouscompound (XXI), where X₃ is a good leaving group, to produce the olefin(XXII). The phosphorous compounds (XXI) are known to those skilled inthe art. It is preferred that X₃ is C₁-C₃ alkyl; it is more preferredthat X₃ is C₁ alkyl. The aldehyde (XX) and the phosphate (XXI) arecombined in an organic solvent then cooled to about 0°. A base such asDBU or TMG is added and the contents of the reaction mixture are warmedto about 20-25° and stirred until the reaction is complete. Once thereaction is complete, it is preferred to separate the E- and Z-olefinisomers (XXII). The separation is done by methods known to those skilledin the art, such as by silica gel chromatography. Next the olefin (XXII)is hydrogenated with a suitable hydrogenation catalyst to obtain thedesired ester (II). Some hydrogenation reactions will give racemic ester(II). The desired stereochemistry of the ester (II) is (S)-, andtherefore it is preferable to use the Z-olefin (XXII) with ahydrogenation catalyst. It is preferred that the hydrogenation catalystis a compound of the formula [Rh(diene)L]⁺X⁻

[0763] where Rh is rhodium;

[0764] where diene is cyclootediene and nonbornadiene;

[0765] where L is DIPMAP, MeDuPhos, EtDuPhos, Binaphane, f-Binaphane,Me-KetalPhos, Me-f-KetalPhos, BINAP, DIOP, BPPFA, BPPM, CHIRAPHOS,PROPHOS, NORPHOS, CYCLOPHOS, BDPP, DEGPHOS, PNNP and where X is ClO₄ ⁻,BF₄ ⁻, CF₃—SO₃ ⁻, Cl⁻, Br⁻, PF₆ ⁻ and SbF₆ ⁻. It is preferred that thehydrogenation catalyst be either DIPMAP or EtDuPhos. Suitable solventsinclude polar solvents such as alcohols, preferably C₁-C₅ alcohols andTHF, more preferably methanol, ethanol, isopropanol and THF. The chiralhydrogenation is performed in a temperature range of from about −20° toabout reflux. It is preferred that the reaction be performed in thetemperature range from about 0° to about room temperature (25°). Thechiral hydrogenation is performed under a pressure of from about oneatmosphere to about 100 psig; it is more preferred that the chiralhydrogenation be performed under a pressure of from about 10 psig toabout 40 psig.

[0766] The (S)-protected ester (II) is then transformed to thecorresponding (S)-protected ketone (III) by reaction with a slightexcess of a compound of the formula CH₂ClX² where X² is —Br and —I inone of two different ways. In one process, no exogenous nucleophile isused. That process requires (1) the presence of three or moreequivalents of strong base which has a pK_(b) of greater than about 30followed by (2) adding acid. The other process requires (1) the presenceof about 2 to about 2.5 equivalents of strong base which has a pK_(b) ofgreater than about 30, (2) contacting the mixture of step (1) with about1 to about 1.5 equivalents of an exogenous nucleophile and (3) addingacid. Suitable strong bases are those which has a pK_(b) of greater thanabout 30. It is preferred that the strong base be selected from thegroup consisting of LDA, LiHMDS and KHMDS; it is more preferred that thestrong base be LDA. Suitable acids are those, which have a pk_(a) ofless than about 10. It is preferred the acid be selected from the groupconsisting of acetic, sulfuric, hydrochloric, citric, phosphoric andbenzoic acids; it is more preferred that the acid be acetic acid. Thepreferred solvent for the process is THF. The reaction can be performedin the temperature range from about −80° to about −50°; it is preferredto perform the reaction in the temperature range of from about −75° toabout −65°. Suitable nucleophiles include alkyl lithium, aryl lithium,alkyl-Grignard and aryl-Grignard reagents. It is preferred that thenucleophile be selected from the group consisting of phenyl lithium,n-butyl lithium, methyl magnesium bromide, methyl magnesium chloride,phenyl magnesium bromide, phenyl magnesium chloride; it is morepreferred that the nucleophile be n-butyl lithium.

[0767] The (S)-protected ketone (III) is then reduced to thecorresponding (S)-alcohol (IV) by means known to those skilled in theart for reduction of a ketone to the corresponding secondary alcohol.The means and reaction conditions for reducing the (S)-protectedcompound (III) to the corresponding alcohol (IV) include, for example,sodium borohydride, lithium borohydride, borane, diisobutylaluminumhydride, zinc borohydride and lithium aluminium hydride. Sodiumborohydride is the preferred reducing agent. The reductions are carriedout for a period of time between about 1 hour and about 3 days attemperatures ranging from about −78° to elevated temperature up to thereflux point of the solvent employed. It is preferred to conduct thereduction between about −78° and about 0°. If borane is used, it may beemployed as a complex, for example, borane-methyl sulfide complex,borane-piperidine complex, or borane-tetrahydrofuran complex. Thepreferred combination of reducing agents and reaction conditions neededare known to those skilled in the art, see for example, Larock, R. C. inComprehensive Organic Transformations, VCH Publishers, 1989. Thereduction of the (S)-protected compound (III) to the correspondingalcohol (IV) produces a second chiral center. The reduction of the(S)-protected compound (III) produces a mixture of diastereomers at thesecond center, (S, R/S)-alcohol (IV). This diastereomeric mixture isthen separated by means known to those skilled in the art such asselective low-temperature recrystallization or chromatographicseparation, most preferably by recrystallization or by employingcommercially available chiral columns. The diastereomer that is used inthe remainder of the process of SCHEME A is the (S,S)-alcohol (IV) sincethis stereochemistry will give the desired epoxide (V).

[0768] The alcohol (IV) is transformed to the corresponding epoxide (V)by means known to those skilled in the art. The stereochemistry of the(S)-(IV) center is maintained in forming the epoxide (V). A preferredmeans is by reaction with base, for example, but not limited to,hydroxide ion generated from sodium hydroxide, potassium hydroxide,lithium hydroxide and the like. Reaction conditions include the use ofC₁-C₆ alcohol solvents; ethanol is preferred. A common co-solvent, suchas for example, ethyl acetate may also be employed. Reactions areconducted at temperatures ranging from about −45° up to the refluxtemperature of the alcohol employed; preferred temperature ranges arebetween about −20° and about 40°.

[0769] The epoxide (V) is then reacted with the appropriatelysubstituted C-terminal amine, R_(C)—NH₂ (VI) by means known to thoseskilled in the art which opens the epoxide to produce the desiredcorresponding enantiomerically pure (S,R)-protected alcohol (VII). Thesubstituted C-terminal amines, R_(C)—NH₂ (VI) of this invention arecommercially available or are known to those skilled in the art and canbe readily prepared from known compounds. It is preferred that whenR_(C) is phenyl, it is substituted in the 3-position or 3,5-positions.

[0770] Suitable reaction conditions for opening the epoxide (V) includerunning the reaction in a wide range of common and inert solvents. C₁-C₆alcohol solvents are preferred and isopropyl alcohol most preferred. Thereactions can be run at temperatures ranging from 20-25° up to thereflux temperature of the alcohol employed. The preferred temperaturerange for conducting the reaction is between 50° up to the refluxtemperature of the alcohol employed. When the substituted C-terminalamine (VI) is a 1-amino-3,5-cis-dimethyl cyclohexyldicarboxylate it ispreferably prepared as follows. To dimethyl-5-isophthalate in aceticacid and methanol, is added rhodium in alumina in a high-pressurebottle. The bottle is saturated with hydrogen at 55 psi and shaken forone week of time. The mixture is then filtered through a thick layer ofcelite cake and rinsed with methanol three times, the solvents areremoved under reduced pressure (with heat) to give a concentrate. Theconcentrate is triturated with ether and filtered again to give thedesired C-terminal amine (VI). When the substituted C-terminal amine(VI) is 1-amino-3,5-cis-dimethoxy cyclohexane it is preferably followingthe general procedure above and making non-critical variations butstarting with 3,5-dimethoxyaniline.

[0771] When the substituted C-terminal amine (VI) is an aminomethylgroup where the substituent on the methyl group is an aryl group, forexample NH₂—CH₂-aryl, is not commercially available it is preferablyprepared as follows. A suitable starting material is the (appropriatelysubstituted) aralkyl compound. The first step is bromination of thealkyl substituent via methods known to those skilled in the art, see forexample R. C. Larock in Comprehensive Organic Transformations, VCHPublishers, 1989, p. 313. Next the alkyl halide is reacted with azide toproduce the aryl-(alkyl)-azide. Last the azide is reduced to thecorresponding amine by hydrogen/catalyst to give the C-terminal amine(VI) of formula NH₂—CH₂—R_(C-aryl).

[0772] SCHEME B discloses an alternative process for production of theenantiomerically pure (S,R)-protected alcohol (VII) from the(S)-protected compound (III). In the alternative process, the(S)-protected compound (III) is first reacted with the appropriatelysubstituted C-terminal amine R_(C)—NH₂ (VI) using the preferredconditions described above to produce the corresponding (S)-protectedketone (XI) which is then reduced using the preferred conditionsdescribed above to produce the corresponding (S,R)-protected alcohol(VII).

[0773] SCHEME C discloses another alternative process for production ofenantiomerically pure (S,R)-protected alcohol (VII) but this time fromthe epoxide (V). In the process of SCHEME C, the epoxide (V) is reactedwith azide to produce the corresponding enantiomerically pure(S,R)-protected azide (XII). Conditions to conduct the azide mediatedepoxide opening are known to those skilled in the art, see for example,J. March, Advanced Organic Chemistry, 3^(rd) Edition, John Wiley & SonsPublishers, 1985, p. 380. Next, the (S,R)-protected azide (XII) isreduced to the corresponding protected amine (XIII) by methods known tothose skilled in the art. Preferred reducing conditions to reduce the(S,R)-protected azide (XII) in the presence of a t-butoxycarbonylN-protecting group include catalytic hydrogenation, the conditions forwhich are known to those skilled in the art. Alternative reducingconditions which may be used to avoid N-deprotection with protectinggroups other than t-butoxycarbonyl are known to those skilled in theart, see for example, R. C. Larock in Comprehensive OrganicTransformations, VCH Publishers, 1989, p. 409. Last, the (S,R)-amine(XIII) is transformed to the corresponding protected alcohol (VII) bynitrogen alkylation with a compound of the formula R_(C)—X₃—X₃ is anappropriate leaving group, such as but not limited to, —Cl, —Br, —I,—O-mesylate, —O-tosylate, O-triflate, etc. X₃ may also be an aldehyde;the corresponding coupling with (XIII) via the known reductive aminationprocedure gives the protected (S,R)-alcohol (VII).

[0774] In the formation of compounds of formula (I), the protectedalcohol (VII) is reacted with an appropriately substituted amide formingagent (IX) such as, for example, an anhydride, acyl halide, or acid ofthe formulas (R_(N))₂O or R_(N)X or R_(N)OH (IX) respectively, by meansknown to those skilled in the art to produce the corresponding(S,R)-substituted amine (IA). Nitrogen acylation conditions for reactionof the alcohol (VII) with an amide forming agent (IX) to produce thecorresponding compound (IA) are known to those skilled in the art andcan be found, for example, in R. C. Larock in Comprehensive OrganicTransformations, VCH Publishers, 1989, p. 981, 979, and 972. The(S,R)-protected amine (IA) is deprotected to the corresponding compounds(I) by means known to those skilled in the art for removal of amineprotecting group. Suitable means for removal of the amine protectinggroup depend on the nature of the protecting group. Those skilled in theart, knowing the nature of a specific protecting group, know whichreagent is preferable for its removal. For example, it is preferred toremove the preferred protecting group, BOC, by dissolving the(S,R)-protected amine (IA) in a trifluoroacetic acid/dichloromethane(1/1) mixture. When complete, the solvents are removed under reducedpressure to give the corresponding (S,R)-amine (I) (as the correspondingsalt, i.e. trifluoroacetic acid salt) which is used without furtherpurification. However, if desired, the (S,R)-amine (I) can be purifiedfurther by means known to those skilled in the art, such as for example,recrystallization. Further, if the non-salt form is desired that alsocan be obtained by means known to those skilled in the art, such as forexample, preparing the free base amine via treatment of the salt withmild basic conditions. Additional BOC deprotection conditions anddeprotection conditions for other protecting groups can be found in T.W. Green and P. G. M. Wuts in “Protective Groups in Organic Chemistry,John Wiley and Sons, 1991, p. 309. Suitable chemically suitable saltsinclude trifluoroacetate, and the anion of mineral acids such aschloride, sulfate, phosphate; preferred is trifluoroacetate.

[0775] In the formation of compounds of formula (X), alcohol (VII) isfurther protected as described above to form the diprotectred compound(XB). Compound (XB) is then reacted with an appropriately substitutedamide forming agent (IX) to form compound (XA), as described above forcompound (IA). Deprotection of (XA) to compunds (X) is conducted asdescribed for the transformation of compound (IA) to compounds (I).

[0776] The protection of amines is conducted, where appropriate, bymethods known to those skilled in the art. Amino protecting groups areknown to those skilled in the art. See for example, “Protecting Groupsin Organic Synthesis”, John Wiley and sons, New York, N.Y., 1981,Chapter 7; “Protecting Groups in Organic Chemistry”, Plenum Press, NewYork, N.Y., 1973, Chapter 2. When the amino protecting group is nolonger needed, it is removed by methods known to those skilled in theart. By definition the amino protecting group must be readily removable.A variety of suitable methodologies are known to those skilled in theart; see also T. W. Green and P. G. M. Wuts in “Protective Groups inOrganic Chemistry, John Wiley and Sons, 1991. Suitable amino protectinggroups include t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl,phthalimido, trichloroacetyl, chloroacetyl, bromoacetyl, iodoacetyl,4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl,4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl,4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl,2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl,4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl,4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl,2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl,1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl,2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl,1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl,1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl,2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl,2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl,2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl,1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl,5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl,2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl,cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl,isobrornyloxycarbonyl, 1-piperidyloxycarbonyl, 9-fluoroenylmethylcarbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.

[0777] It is preferred that the protecting group be t-butoxycarbonyl(BOC) and/or benzyloxycarbonyl (CBZ), it is more preferred that theprotecting group be t-butoxycarbonyl. One skilled in the art willrecognize suitable methods of introducing a t-butoxycarbonyl orbenzyloxycarbonyl protecting group and may additionally consult T. W.Green and P. G. M. Wuts in “Protective Groups in Organic Chemistry, JohnWiley and Sons, 1991 for guidance.

[0778] The compounds of the invention may contain geometric or opticalisomers as well as tautomers. Thus, the invention includes all tautomersand pure geometric isomers, such as the E and Z geometric isomers, aswell as mixtures thereof. Further, the invention includes pureenantiomers and diastereomers as well as mixtures thereof, includingracemic mixtures. The individual geometric isomers, enantiomers ordiastereomers may be prepared or isolated by methods known to thoseskilled in the art, including but not limited to chiral chromatography;preparing diastereomers, separating the diastereomers and converting thediastereomers into enantiomers through the use of a chiral resolvingagent.

[0779] Compounds of the invention with designated stereochemistry can beincluded in mixtures, including racemic mixtures, with otherenantiomers, diastereomers, geometric isomers or tautomers. In apreferred aspect, compounds of the invention with (S, R, R), (S, S, S),or (S, R, S) stereochemistry are typically present in these mixtures inexcess of 50 percent. Preferably, compounds of the invention withdesignated stereochemistry are present in these mixtures in excess of 80percent. More preferably, compounds of the invention with designatedstereochemistry are present in these mixtures in excess of 90 percent.Even more preferably, compounds of the invention with designatedstereochemistry are present in these mixtures in excess of 99 percent.

[0780] The invention encompasses pharmaceutically acceptable salts ofthe compounds of formula (AA), (I) and (X). Pharmaceutically acceptablesalts are preferred over the corresponding amines of formula (AA), (I)or (X) since they produce compounds which are more water soluble, stableand/or more crystalline. Pharmaceutically acceptable salts are any saltwhich retains the activity of the parent compound and does not impartany deleterious or undesirable effect on the subject to whom it isadministered and in the context in which it is administered.Pharmaceutically acceptable salts include salts of both inorganic andorganic acids. The preferred pharmaceutically acceptable salts includesalts of the following acids acetic, aspartic, benzenesulfonic, benzoic,bicarbonic, bisulfuric, bitartaric, butyric, calcium edetate, camsylic,carbonic, chlorobenzoic, citric, edetic, edisylic, estolic, esyl,esylic, formic, fumaric, gluceptic, gluconic, glutamic,glycollylarsanilic, hexamic, hexylresorcinoic, hydrabamic, hydrobromic,hydrochloric, hydroiodic, hydroxynaphthoic, isethionic, lactic,lactobionic, maleic, malic, malonic, mandelic, methanesulfonic,methylnitric, methylsulfuric, mucic, muconic, napsylic, nitric, oxalic,p-nitromethanesulfonic, pamoic, pantothenic, phosphoric, monohydrogenphosphoric, dihydrogen phosphoric, phthalic, polygalactouronic,propionic, salicylic, stearic, succinic, succinic, sulfamic, sulfanilic,sulfonic, sulfuric, tannic, tartaric, teoclic and toluenesulfonic. Forother acceptable salts, see Int. J. Pharm., 33, 201-217 (1986) and J.Pharm. Sci., 66(1), 1, (1977).

[0781] The invention provides compounds, compositions, kits, and methodsfor inhibiting beta-secretase enzyme activity and A beta peptideproduction. Inhibition of beta-secretase enzyme activity halts orreduces the production of A beta from APP and reduces or eliminates theformation of beta-amyloid deposits in the brain.

[0782] Methods of the Invention

[0783] The compounds of the invention, and pharmaceutically acceptablesalts thereof, are useful for treating humans or animals suffering froma condition characterized by a pathological form of beta-amyloidpeptide, such as beta-amyloid plaques, and for helping to prevent ordelay the onset of such a condition.

[0784] As used herein, the term “treating” means that the compounds ofthe invention can be used in humans with at least a tentative diagnosisof disease. The compounds of the invention will delay or slow theprogression of the disease thereby giving the individual a more usefullife span.

[0785] The term “preventing” means that the compounds of the inventionare useful when administered to a patient who has not been diagnosed aspossibly having the disease at the time of administration, but who wouldnormally be expected to develop the disease or be at increased risk forthe disease. The compounds of the invention will slow the development ofdisease symptoms, delay the onset of the disease, or prevent theindividual from developing the disease at all. Preventing also includesadministration of the compounds of the invention to those individualsthought to be predisposed to the disease due to age, familial history,genetic or chromosomal abnormalities, and/or due to the presence of oneor more biological markers for the disease, such as a known geneticmutation of APP or APP cleavage products in brain tissues or fluids.

[0786] In treating or preventing the above diseases, the compounds ofthe invention are administered in a therapeutically effective amount.The therapeutically effective amount will vary depending on theparticular compound used and the route of administration, as is known tothose skilled in the art.

[0787] In treating a patient displaying any of the diagnosed aboveconditions a physician may administer a compound of the inventionimmediately and continue administration indefinitely, as needed. Intreating patients who are not diagnosed as having Alzheimer's disease,but who are believed to be at substantial risk for Alzheimer's disease,the physician should preferably start treatment when the patient firstexperiences early pre-Alzheimer's symptoms such as, memory or cognitiveproblems associated with aging. In addition, there are some patients whomay be determined to be at risk for developing Alzheimer's through thedetection of a genetic marker such as APOE4 or other biologicalindicators that are predictive for Alzheimer's disease. In thesesituations, even though the patient does not have symptoms of thedisease, administration of the compounds of the invention may be startedbefore symptoms appear, and treatment may be continued indefinitely toprevent or delay the onset of the disease.

[0788] Dosage Forms and Amounts

[0789] The compounds of the invention can be administered orally,parenterally, (IV, IM, depo-IM, SQ, and depo SQ), sublingually,intranasally (inhalation), intrathecally, topically, or rectally. Dosageforms known to those of skill in the art are suitable for delivery ofthe compounds of the invention.

[0790] Compositions are provided that contain therapeutically effectiveamounts of the compounds of the invention. The compounds are preferablyformulated into suitable pharmaceutical preparations such as tablets,capsules, or elixirs for oral administration or in sterile solutions orsuspensions for parenteral administration. Typically the compoundsdescribed above are formulated into pharmaceutical compositions usingtechniques and procedures well known in the art.

[0791] About 1 to 500 mg of a compound or mixture of compounds of theinvention or a physiologically acceptable salt or ester is compoundedwith a physiologically acceptable vehicle, carrier, excipient, binder,preservative, stabilizer, flavor, etc., in a unit dosage form as calledfor by accepted pharmaceutical practice. The amount of active substancein those compositions or preparations is such that a suitable dosage inthe range indicated is obtained. The compositions are preferablyformulated in a unit dosage form, each dosage containing from about 2 toabout 100 mg, more preferably about 10 to about 30 mg of the activeingredient. The term “unit dosage from” refers to physically discreteunits suitable as unitary dosages for human subjects and other mammals,each unit containing a predetermined quantity of active materialcalculated to produce the desired therapeutic effect, in associationwith a suitable pharmaceutical excipient.

[0792] To prepare compositions, one or more compounds of the inventionare mixed with a suitable pharmaceutically acceptable carrier. Uponmixing or addition of the compound(s), the resulting mixture may be asolution, suspension, emulsion, or the like. Liposomal suspensions mayalso be suitable as pharmaceutically acceptable carriers. These may beprepared according to methods known to those skilled in the art. Theform of the resulting mixture depends upon a number of factors,including the intended mode of administration and the solubility of thecompound in the selected carrier or vehicle. The effective concentrationis sufficient for lessening or ameliorating at least one symptom of thedisease, disorder, or condition treated and may be empiricallydetermined.

[0793] Pharmaceutical carriers or vehicles suitable for administrationof the compounds provided herein include any such carriers known tothose skilled in the art to be suitable for the particular mode ofadministration. In addition, the active materials can also be mixed withother active materials that do not impair the desired action, or withmaterials that supplement the desired action, or have another action.The compounds may be formulated as the sole pharmaceutically activeingredient in the composition or may be combined with other activeingredients.

[0794] Where the compounds exhibit insufficient solubility, methods forsolubilizing may be used. Such methods are known and include, but arenot limited to, using cosolvents such as dimethylsulfoxide (DMSO), usingsurfactants such as Tween®, and dissolution in aqueous sodiumbicarbonate. Derivatives of the compounds, such as salts or prodrugs mayalso be used in formulating effective pharmaceutical compositions.

[0795] The concentration of the compound is effective for delivery of anamount upon administration that lessens or ameliorates at least onesymptom of the disorder for which the compound is administered.Typically, the compositions are formulated for single dosageadministration.

[0796] The compounds of the invention may be prepared with carriers thatprotect them against rapid elimination from the body, such astime-release formulations or coatings. Such carriers include controlledrelease formulations, such as, but not limited to, microencapsulateddelivery systems. The active compound is included in thepharmaceutically acceptable carrier in an amount sufficient to exert atherapeutically useful effect in the absence of undesirable side effectson the patient treated. The therapeutically effective concentration maybe determined empirically by testing the compounds in known in vitro andin vivo model systems for the treated disorder.

[0797] The compounds and compositions of the invention can be enclosedin multiple or single dose containers. The enclosed compounds andcompositions can be provided in kits, for example, including componentparts that can be assembled for use. For example, a compound inhibitorin lyophilized form and a suitable diluent may be provided as separatedcomponents for combination prior to use. A kit may include a compoundinhibitor and a second therapeutic agent for co-administration. Theinhibitor and second therapeutic agent may be provided as separatecomponent parts. A kit may include a plurality of containers, eachcontainer holding one or more unit dose of the compound of theinvention. The containers are preferably adapted for the desired mode ofadministration, including, but not limited to tablets, gel capsules,sustained-release capsules, and the like for oral administration; depotproducts, pre-filled syringes, ampoules, vials, and the like forparenteral administration; and patches, medipads, creams, and the likefor topical administration.

[0798] The concentration of active compound in the drug composition willdepend on absorption, inactivation, and excretion rates of the activecompound, the dosage schedule, and amount administered as well as otherfactors known to those of skill in the art.

[0799] The active ingredient may be administered at once, or may bedivided into a number of smaller doses to be administered at intervalsof time. It is understood that the precise dosage and duration oftreatment is a function of the disease being treated and may bedetermined empirically using known testing protocols or by extrapolationfrom in vivo or in vitro test data. It is to be noted thatconcentrations and dosage values may also vary with the severity of thecondition to be alleviated. It is to be further understood that for anyparticular subject, specific dosage regimens should be adjusted overtime according to the individual need and the professional judgment ofthe person administering or supervising the administration of thecompositions, and that the concentration ranges set forth herein areexemplary only and are not intended to limit the scope or practice ofthe claimed compositions.

[0800] If oral administration is desired, the compound should beprovided in a composition that protects it from the acidic environmentof the stomach. For example, the composition can be formulated in anenteric coating that maintains its integrity in the stomach and releasesthe active compound in the intestine. The composition may also beformulated in combination with an antacid or other such ingredient.

[0801] Oral compositions will generally include an inert diluent or anedible carrier and may be compressed into tablets or enclosed in gelatincapsules. For the purpose of oral therapeutic administration, the activecompound or compounds can be incorporated with excipients and used inthe form of tablets, capsules, or troches. Pharmaceutically compatiblebinding agents and adjuvant materials can be included as part of thecomposition.

[0802] The tablets, pills, capsules, troches, and the like can containany of the following ingredients or compounds of a similar nature: abinder such as, but not limited to, gum tragacanth, acacia, corn starch,or gelatin; an excipient such as microcrystalline cellulose, starch, orlactose; a disintegrating agent such as, but not limited to, alginicacid and corn starch; a lubricant such as, but not limited to, magnesiumstearate; a gildant, such as, but not limited to, colloidal silicondioxide; a sweetening agent such as sucrose or saccharin; and aflavoring agent such as peppermint, methyl salicylate, or fruitflavoring.

[0803] When the dosage unit form is a capsule, it can contain, inaddition to material of the above type, a liquid carrier such as a fattyoil. In addition, dosage unit forms can contain various other materials,which modify the physical form of the dosage unit, for example, coatingsof sugar and other enteric agents. The compounds can also beadministered as a component of an elixir, suspension, syrup, wafer,chewing gum or the like. A syrup may contain, in addition to the activecompounds, sucrose as a sweetening agent and certain preservatives, dyesand colorings, and flavors.

[0804] The active materials can also be mixed with other activematerials that do not impair the desired action, or with materials thatsupplement the desired action.

[0805] Solutions or suspensions used for parenteral, intradermal,subcutaneous, or topical application can include any of the followingcomponents: a sterile diluent such as water for injection, salinesolution, fixed oil, a naturally occurring vegetable oil such as sesameoil, coconut oil, peanut oil, cottonseed oil, and the like, or asynthetic fatty vehicle such as ethyl oleate, and the like, polyethyleneglycol, glycerine, propylene glycol, or other synthetic solvent;antimicrobial agents such as benzyl alcohol and methyl parabens;antioxidants such as ascorbic acid and sodium bisulfite; chelatingagents such as ethylenediaminetetraacetic acid (EDTA); buffers such asacetates, citrates, and phosphates; and agents for the adjustment oftonicity such as sodium chloride and dextrose. Parenteral preparationscan be enclosed in ampoules, disposable syringes, or multiple dose vialsmade of glass, plastic, or other suitable material. Buffers,preservatives, antioxidants, and the like can be incorporated asrequired.

[0806] Where administered intravenously, suitable carriers includephysiological saline, phosphate buffered saline (PBS), and solutionscontaining thickening and solubilizing agents such as glucose,polyethylene glycol, polypropyleneglycol, and mixtures thereof.Liposomal suspensions including tissue-targeted liposomes may also besuitable as pharmaceutically acceptable carriers. These may be preparedaccording to methods known for example, as described in U.S. Pat. No.4,522,811.

[0807] The active compounds may be prepared with carriers that protectthe compound against rapid elimination from the body, such astime-release formulations or coatings. Such carriers include controlledrelease formulations, such as, but not limited to, implants andmicroencapsulated delivery systems, and biodegradable, biocompatiblepolymers such as collagen, ethylene vinyl acetate, polyanhydrides,polyglycolic acid, polyorthoesters, polylactic acid, and the like.Methods for preparation of such formulations are known to those skilledin the art.

[0808] The compounds of the invention can be administered orally,parenterally (IV, IM, depo-IM, SQ, and depo-SQ), sublingually,intranasally (inhalation), intrathecally, topically, or rectally. Dosageforms known to those skilled in the art are suitable for delivery of thecompounds of the invention.

[0809] Compounds of the invention may be administered enterally orparenterally. When administered orally, compounds of the invention canbe administered in usual dosage forms for oral administration as is wellknown to those skilled in the art. These dosage forms include the usualsolid unit dosage forms of tablets and capsules as well as liquid dosageforms such as solutions, suspensions, and elixirs. When the solid dosageforms are used, it is preferred that they be of the sustained releasetype so that the compounds of the invention need to be administered onlyonce or twice daily.

[0810] The oral dosage forms are administered to the patient 1, 2, 3, or4 times daily. It is preferred that the compounds of the invention beadministered either three or fewer times, more preferably once or twicedaily. Hence, it is preferred that the compounds of the invention beadministered in oral dosage form. It is preferred that whatever oraldosage form is used, that it be designed so as to protect the compoundsof the invention from the acidic environment of the stomach. Entericcoated tablets are well known to those skilled in the art. In addition,capsules filled with small spheres each coated to protect from theacidic stomach, are also well known to those skilled in the art.

[0811] When administered orally, an administered amount therapeuticallyeffective to inhibit beta-secretase activity, to inhibit A betaproduction, to inhibit A beta deposition, or to treat or prevent AD isfrom about 0.1 mg/day to about 1,000 mg/day. It is preferred that theoral dosage is from about 1 mg/day to about 100 mg/day. It is morepreferred that the oral dosage is from about 5 mg/day to about 50mg/day. It is understood that while a patient may be started at onedose, that dose may be varied over time as the patient's conditionchanges.

[0812] Compounds of the invention may also be advantageously deliveredin a nano crystal dispersion formulation. Preparation of suchformulations is described, for example, in U.S. Pat. No. 5,145,684. Nanocrystalline dispersions of HIV protease inhibitors and their method ofuse are described in U.S. Pat. No. 6,045,829. The nano crystallineformulations typically afford greater bioavailability of drug compounds.

[0813] The compounds of the invention can be administered parenterally,for example, by IV, IM, depo-IM, SC, or depo-SC. When administeredparenterally, a therapeutically effective amount of about 0.5 to about100 mg/day, preferably from about 5 to about 50 mg daily should bedelivered. When a depot formulation is used for injection once a monthor once every two weeks, the dose should be about 0.5 mg/day to about 50mg/day, or a monthly dose of from about 15 mg to about 1,500 mg. In partbecause of the forgetfulness of the patients with Alzheimer's disease,it is preferred that the parenteral dosage form be a depo formulation.

[0814] The compounds of the invention can be administered sublingually.When given sublingually, the compounds of the invention should be givenone to four times daily in the amounts described above for IMadministration.

[0815] The compounds of the invention can be administered intranasally.When given by this route, the appropriate dosage forms are a nasal sprayor dry powder, as is known to those skilled in the art. The dosage ofthe compounds of the invention for intranasal administration is theamount described above for IM administration.

[0816] The compounds of the invention can be administered intrathecally.When given by this route the appropriate dosage form can be a parenteraldosage form as is known to those skilled in the art. The dosage of thecompounds of the invention for intrathecal administration is the amountdescribed above for IM administration.

[0817] The compounds of the invention can be administered topically.When given by this route, the appropriate dosage form is a cream,ointment, or patch. Because of the amount of the compounds of theinvention to be administered, the patch is preferred. When administeredtopically, the dosage is from about 0.5 mg/day to about 200 mg/day.Because the amount that can be delivered by a patch is limited, two ormore patches may be used. The number and size of the patch is notimportant, what is important is that a therapeutically effective amountof the compounds of the invention be delivered as is known to thoseskilled in the art. The compounds of the invention can be administeredrectally by suppository as is known to those skilled in the art. Whenadministered by suppository, the therapeutically effective amount isfrom about 0.5 mg to about 500 mg.

[0818] The compounds of the invention can be administered by implants asis known to those skilled in the art. When administering a compound ofthe invention by implant, the therapeutically effective amount is theamount described above for depot administration.

[0819] Given a particular compound of the invention and a desired dosageform, one skilled in the art would know how to prepare and administerthe appropriate dosage form.

[0820] The compounds of the invention are used in the same manner, bythe same routes of administration, using the same pharmaceutical dosageforms, and at the same dosing schedule as described above, forpreventing disease or treating patients with MCI (mild cognitiveimpairment) and preventing or delaying the onset of Alzheimer's diseasein those who would progress from MCI to AD, for treating or preventingDown's syndrome, for treating humans who have Hereditary CerebralHemorrhage with Amyloidosis of the Dutch-Type, for treating cerebralamyloid angiopathy and preventing its potential consequences, i.e.single and recurrent lobar hemorrhages, for treating other degenerativedementias, including dementias of mixed vascular and degenerativeorigin, dementia associated with Parkinson's disease, dementiaassociated with progressive supranuclear palsy, dementia associated withcortical basal degeneration, and diffuse Lewy body type of Alzheimer'sdisease.

[0821] The compounds of the invention can be used in combination, witheach other or with other therapeutic agents or approaches used to treator prevent the conditions listed above. Such agents or approachesinclude: acetylcholine esterase inhibitors such as tacrine(tetrahydroaminoacridine, marketed as COGNEX®), donepezil hydrochloride,(marketed as Aricept® and rivastigmine (marketed as Exelon®);gamma-secretase inhibitors; anti-inflammatory agents such ascyclooxygenase II inhibitors; anti-oxidants such as Vitamin E andginkolides; immunological approaches, such as, for example, immunizationwith A beta peptide or administration of anti-A beta peptide antibodies;statins; and direct or indirect neurotropic agents such asCerebrolysin®, AIT-082 (Emilieu, 2000, Arch. Neurol. 57:454), and otherneurotropic agents of the future.

[0822] In addition, the compounds of formula (AA), (I) or (X) can alsobe used with inhibitors of P-glycoprotein (P-gp). P-gp inhibitors andthe use of such compounds are known to those skilled in the art. See forexample, Cancer Research, 53, 4595-4602 (1993), Clin. Cancer Res., 2,7-12 (1996), Cancer Research, 56, 4171-4179 (1996), InternationalPublications WO99/64001 and WO01/10387. The important thing is that theblood level of the P-gp inhibitor be such that it exerts its effect ininhibiting P-gp from decreasing brain blood levels of the compounds offormula (A). To that end the P-gp inhibitor and the compounds of formula(A) can be administered at the same time, by the same or different routeof administration, or at different times. The important thing is not thetime of administration but having an effective blood level of the P-gpinhibitor.

[0823] Suitable P-gp inhibitors include cyclosporin A, verapamil,tamoxifen, quinidine, Vitamin E-TGPS, ritonavir, megestrol acetate,progesterone, rapamycin, 10,11-methanodibenzosuberane, phenothiazines,acridine derivatives such as GF120918, FK506, VX-710, LY335979, PSC-833,GF-102,918 and other steroids. It is to be understood that additionalagents will be found that have the same function and therefore achievethe same outcome; such compounds are also considered to be useful.

[0824] The P-gp inhibitors can be administered orally, parenterally,(IV, IM, IM-depo, SQ, SQ-depo), topically, sublingually, rectally,intranasally, intrathecally and by implant.

[0825] The therapeutically effective amount of the P-gp inhibitors isfrom about 0.1 to about 300 mg/kg/day, preferably about 0.1 to about 150mg/kg daily. It is understood that while a patient may be started on onedose, that dose may have to be varied over time as the patient'scondition changes.

[0826] When administered orally, the P-gp inhibitors can be administeredin usual dosage forms for oral administration as is known to thoseskilled in the art. These dosage forms include the usual solid unitdosage forms of tablets and capsules as well as liquid dosage forms suchas solutions, suspensions and elixirs. When the solid dosage forms areused, it is preferred that they be of the sustained release type so thatthe P-gp inhibitors need to be administered only once or twice daily.The oral dosage forms are administered to the patient one thru fourtimes daily. It is preferred that the P-gp inhibitors be administeredeither three or fewer times a day, more preferably once or twice daily.Hence, it is preferred that the P-gp inhibitors be administered in soliddosage form and further it is preferred that the solid dosage form be asustained release form which permits once or twice daily dosing. It ispreferred that what ever dosage form is used, that it be designed so asto protect the P-gp inhibitors from the acidic environment of thestomach. Enteric coated tablets are well known to those skilled in theart. In addition, capsules filled with small spheres each coated toprotect from the acidic stomach, are also well known to those skilled inthe art.

[0827] In addition, the P-gp inhibitors can be administeredparenterally. When administered parenterally they can be administeredIV, IM, depo-IM, SQ or depo-SQ.

[0828] The P-gp inhibitors can be given sublingually. When givensublingually, the P-gp inhibitors should be given one thru four timesdaily in the same amount as for IM administration.

[0829] The P-gp inhibitors can be given intranasally. When given by thisroute of administration, the appropriate dosage forms are a nasal sprayor dry powder as is known to those skilled in the art. The dosage of theP-gp inhibitors for intranasal administration is the same as for IMadministration.

[0830] The P-gp inhibitors can be given intrathecally. When given bythis route of administration the appropriate dosage form can be aparenteral dosage form as is known to those skilled in the art.

[0831] The P-gp inhibitors can be given topically. When given by thisroute of administration, the appropriate dosage form is a cream,ointment or patch. Because of the amount of the P-gp inhibitors neededto be administered the patch is preferred. However, the amount that canbe delivered by a patch is limited. Therefore, two or more patches maybe required. The number and size of the patch is not important, what isimportant is that a therapeutically effective amount of the P-gpinhibitors be delivered as is known to those skilled in the art.

[0832] The P-gp inhibitors can be administered rectally by suppositoryas is known to those skilled in the art.

[0833] The P-gp inhibitors can be administered by implants as is knownto those skilled in the art.

[0834] There is nothing novel about the route of administration nor thedosage forms for administering the P-gp inhibitors. Given a particularP-gp inhibitor, and a desired dosage form, one skilled in the art wouldknow how to prepare the appropriate dosage form for the P-gp inhibitor.

[0835] It should be apparent to one skilled in the art that the exactdosage and frequency of administration will depend on the particularcompounds of the invention administered, the particular condition beingtreated, the severity of the condition being treated, the age, weight,general physical condition of the particular patient, and othermedication the individual may be taking as is well known toadministering physicians who are skilled in this art.

[0836] Inhibition of APP Cleavage

[0837] The compounds of the invention inhibit cleavage of APP betweenMet595 and Asp596 numbered for the APP695 isoform, or a mutant thereof,or at a corresponding site of a different isoform, such as APP751 orAPP770, or a mutant thereof (sometimes referred to as the “betasecretase site”). While not wishing to be bound by a particular theory,inhibition of beta-secretase activity is thought to inhibit productionof beta amyloid peptide (A beta). Inhibitory activity is demonstrated inone of a variety of inhibition assays, whereby cleavage of an APPsubstrate in the presence of a beta-secretase enzyme is analyzed in thepresence of the inhibitory compound, under conditions normallysufficient to result in cleavage at the beta-secretase cleavage site.Reduction of APP cleavage at the beta-secretase cleavage site comparedwith an untreated or inactive control is correlated with inhibitoryactivity. Assay systems that can be used to demonstrate efficacy of thecompound inhibitors of the invention are known. Representative assaysystems are described, for example, in U.S. Pat. Nos. 5,942,400,5,744,346, as well as in the Examples below.

[0838] The enzymatic activity of beta-secretase and the production of Abeta can be analyzed in vitro or in vivo, using natural, mutated, and/orsynthetic APP substrates, natural, mutated, and/or synthetic enzyme, andthe test compound. The analysis may involve primary or secondary cellsexpressing native, mutant, and/or synthetic APP and enzyme, animalmodels expressing native APP and enzyme, or may utilize transgenicanimal models expressing the substrate and enzyme. Detection ofenzymatic activity can be by analysis of one or more of the cleavageproducts, for example, by immunoassay, fluorometric or chromogenicassay, HPLC, or other means of detection. Inhibitory compounds aredetermined as those having the ability to decrease the amount ofbeta-secretase cleavage product produced in comparison to a control,where beta-secretase mediated cleavage in the reaction system isobserved and measured in the absence of inhibitory compounds.

[0839] Beta-Secretase

[0840] Various forms of beta-secretase enzyme are known, and areavailable and useful for assay of enzyme activity and inhibition ofenzyme activity. These include native, recombinant, and synthetic formsof the enzyme. Human beta-secretase is known as Beta Site APP CleavingEnzyme (BACE), Asp2, and memapsin 2, and has been characterized, forexample, in U.S. Pat. No. 5,744,346 and published PCT patentapplications WO98/22597, WO00/03819, WO01/23533, and WO00/17369, as wellas in literature publications (Hussain et al., 1999, Mol. Cell.Neurosci. 14:419-427; Vassar et al., 1999, Science 286:735-741; Yan etal., 1999, Nature 402:533-537; Sinha et al., 1999, Nature 40:537-540;and Lin et al., 2000, PNAS USA 97:1456-1460). Synthetic forms of theenzyme have also been described (WO98/22597 and WO00/17369).Beta-secretase can be extracted and purified from human brain tissue andcan be produced in cells, for example mammalian cells expressingrecombinant enzyme.

[0841] Preferred rearranged compounds are effective to inhibit about 50%of beta-secretase enzymatic activity at a concentration of less than 50micromolar, preferably at a concentration of 10 micromolar or less, morepreferably 1 micromolar or less, and most preferably 10 nanomolar orless.

[0842] APP Substrate

[0843] Assays that demonstrate inhibition of beta-secretase-mediatedcleavage of APP can utilize any of the known forms of APP, including the695 amino acid “normal” isotype described by Kang et al., 1987, Nature325:733-6, the 770 amino acid isotype described by Kitaguchi et. al.,1981, Nature 331:530-532, and variants such as the Swedish Mutation(KM670-1NL) (APP-SW), the London Mutation (V7176F), and others. See, forexample, U.S. Pat. No. 5,766,846 and also Hardy, 1992, Nature Genet.1:233-234, for a review of known variant mutations. Additional usefulsubstrates include the dibasic amino acid modification, APP-KKdisclosed, for example, in WO 00/17369, fragments of APP, and syntheticpeptides containing the beta-secretase cleavage site, wild type (WT) ormutated form, e.g., SW, as described, for example, in U.S. Pat. No.5,942,400 and WO00/03819.

[0844] The APP substrate contains the beta-secretase cleavage site ofAPP (KM-DA or NL-DA) for example, a complete APP peptide or variant, anAPP fragment, a recombinant or synthetic APP, or a fusion peptide.Preferably, the fusion peptide includes the beta-secretase cleavage sitefused to a peptide having a moiety useful for enzymatic assay, forexample, having isolation and/or detection properties. A useful moietymay be an antigenic epitope for antibody binding, a label or otherdetection moiety, a binding substrate, and the like.

[0845] Antibodies

[0846] Products characteristic of APP cleavage can be measured byimmunoassay using various antibodies, as described, for example, inPirttila et al., 1999, Neuro. Lett. 249:21-4, and in U.S. Pat. No.5,612,486. Useful antibodies to detect A beta include, for example, themonoclonal antibody 6E10 (Senetek, St. Louis, Mo.) that specificallyrecognizes an epitope on amino acids 1-16 of the A beta peptide;antibodies 162 and 164 (New York State Institute for Basic Research,Staten Island, N.Y.) that are specific for human A beta 1-40 and 1-42,respectively; and antibodies that recognize the junction region ofbeta-amyloid peptide, the site between residues 16 and 17, as describedin U.S. Pat. No. 5,593,846. Antibodies raised against a syntheticpeptide of residues 591 to 596 of APP and SW192 antibody raised against590-596 of the Swedish mutation are also useful in immunoassay of APPand its cleavage products, as described in U.S. Pat. Nos. 5,604,102 and5,721,130.

[0847] Assay Systems

[0848] Assays for determining APP cleavage at the beta-secretasecleavage site are well known in the art. Exemplary assays, aredescribed, for example, in U.S. Pat. Nos. 5,744,346 and 5,942,400, anddescribed in the Examples below.

[0849] Cell Free Assays

[0850] Exemplary assays that can be used to demonstrate the inhibitoryactivity of the compounds of the invention are described, for example,in WO00/17369, WO 00/03819, and U.S. Pat. No. 5,942,400 and 5,744,346.Such assays can be performed in cell-free incubations or in cellularincubations using cells expressing a beta-secretase and an APP substratehaving a beta-secretase cleavage site.

[0851] An APP substrate containing the beta-secretase cleavage site ofAPP, for example, a complete APP or variant, an APP fragment, or arecombinant or synthetic APP substrate containing the amino acidsequence: KM-DA or NL-DA, is incubated in the presence of beta-secretaseenzyme, a fragment thereof, or a synthetic or recombinant polypeptidevariant having beta-secretase activity and effective to cleave thebeta-secretase cleavage site of APP, under incubation conditionssuitable for the cleavage activity of the enzyme. Suitable substratesoptionally include derivatives that may be fusion proteins or peptidesthat contain the substrate peptide and a modification useful tofacilitate the purification or detection of the peptide or itsbeta-secretase cleavage products. Useful modifications include theinsertion of a known antigenic epitope for antibody binding; the linkingof a label or detectable moiety, the linking of a binding substrate, andthe like.

[0852] Suitable incubation conditions for a cell-free in vitro assayinclude, for example: approximately 200 nanomolar to 10 micromolarsubstrate, approximately 10 to 200 picomolar enzyme, and approximately0.1 nanomolar to 10 micromolar inhibitor compound, in aqueous solution,at an approximate pH of 4-7, at approximately 37 degrees C., for a timeperiod of approximately 10 minutes to 3 hours. These incubationconditions are exemplary only, and can be varied as required for theparticular assay components and/or desired measurement system.Optimization of the incubation conditions for the particular assaycomponents should account for the specific beta-secretase enzyme usedand its pH optimum, any additional enzymes and/or markers that might beused in the assay, and the like. Such optimization is routine and willnot require undue experimentation.

[0853] One useful assay utilizes a fusion peptide having maltose bindingprotein (MBP) fused to the C-terminal 125 amino acids of APP-SW. The MBPportion is captured on an assay substrate by anti-MBP capture antibody.Incubation of the captured fusion protein in the presence ofbeta-secretase results in cleavage of the substrate at thebeta-secretase cleavage site. Analysis of the cleavage activity can be,for example, by immunoassay of cleavage products. One such immunoassaydetects a unique epitope exposed at the carboxy terminus of the cleavedfusion protein, for example, using the antibody SW192. This assay isdescribed, for example, in U.S. Pat. No. 5,942,400.

[0854] Cellular Assay

[0855] Numerous cell-based assays can be used to analyze beta-secretaseactivity and/or processing of APP to release A beta. Contact of an APPsubstrate with a beta-secretase enzyme within the cell and in thepresence or absence of a compound inhibitor of the invention can be usedto demonstrate beta-secretase inhibitory activity of the compound.Preferably, assay in the presence of a useful inhibitory compoundprovides at least about 30%, most preferably at least about 50%inhibition of the enzymatic activity, as compared with a non-inhibitedcontrol.

[0856] In one embodiment, cells that naturally express beta-secretaseare used. Alternatively, cells are modified to express a recombinantbeta-secretase or synthetic variant enzyme as discussed above. The APPsubstrate may be added to the culture medium and is preferably expressedin the cells. Cells that naturally express APP, variant or mutant formsof APP, or cells transformed to express an isoform of APP, mutant orvariant APP, recombinant or synthetic APP, APP fragment, or syntheticAPP peptide or fusion protein containing the beta-secretase APP cleavagesite can be used, provided that the expressed APP is permitted tocontact the enzyme and enzymatic cleavage activity can be analyzed.

[0857] Human cell lines that normally process A beta from APP provide auseful means to assay inhibitory activities of the compounds of theinvention. Production and release of A beta and/or other cleavageproducts into the culture medium can be measured, for example byimmunoassay, such as Western blot or enzyme-linked immunoassay (EIA)such as by ELISA.

[0858] Cells expressing an APP substrate and an active beta-secretasecan be incubated in the presence of a compound inhibitor to demonstrateinhibition of enzymatic activity as compared with a control. Activity ofbeta-secretase can be measured by analysis of one or more cleavageproducts of the APP substrate. For example, inhibition of beta-secretaseactivity against the substrate APP would be expected to decrease releaseof specific beta-secretase induced APP cleavage products such as A beta.

[0859] Although both neural and non-neural cells process and release Abeta, levels of endogenous beta-secretase activity are low and oftendifficult to detect by EIA. The use of cell types known to have enhancedbeta-secretase activity, enhanced processing of APP to A beta, and/orenhanced production of A beta are therefore preferred. For example,transfection of cells with the Swedish Mutant form of APP (APP-SW); withAPP-KK; or with APP-SW-KK provides cells having enhanced beta-secretaseactivity and producing amounts of A beta that can be readily measured.

[0860] In such assays, for example, the cells expressing APP andbeta-secretase are incubated in a culture medium under conditionssuitable for beta-secretase enzymatic activity at its cleavage site onthe APP substrate. On exposure of the cells to the compound inhibitor,the amount of A beta released into the medium and/or the amount of CTF99fragments of APP in the cell lysates is reduced as compared with thecontrol. The cleavage products of APP can be analyzed, for example, byimmune reactions with specific antibodies, as discussed above.

[0861] Preferred cells for analysis of beta-secretase activity includeprimary human neuronal cells, primary transgenic animal neuronal cellswhere the transgene is APP, and other cells such as those of a stable293 cell line expressing APP, for example, APP-SW.

[0862] In Vivo Assays: Animal Models

[0863] Various animal models can be used to analyze beta-secretaseactivity and/or processing of APP to release A beta, as described above.For example, transgenic animals expressing APP substrate andbeta-secretase enzyme can be used to demonstrate inhibitory activity ofthe compounds of the invention. Certain transgenic animal models havebeen described, for example, in U.S. Pat. Nos. 5,877,399; 5,612,486;5,387,742; 5,720,936; 5,850,003; 5,877,015, and 5,811,633, and in Ganeset al., 1995, Nature 373:523. Preferred are animals that exhibitcharacteristics associated with the pathophysiology of AD.Administration of the compound inhibitors of the invention to thetransgenic mice described herein provides an alternative method fordemonstrating the inhibitory activity of the compounds. Administrationof the compounds in a pharmaceutically effective carrier and via anadministrative route that reaches the target tissue in an appropriatetherapeutic amount is also preferred.

[0864] Inhibition of beta-secretase mediated cleavage of APP at thebeta-secretase cleavage site and of A beta release can be analyzed inthese animals by measure of cleavage fragments in the animal's bodyfluids such as cerebral fluid or tissues. Analysis of brain tissues forA beta deposits or plaques is preferred.

[0865] On contacting an APP substrate with a beta-secretase enzyme inthe presence of an inhibitory compound of the invention and underconditions sufficient to permit enzymatic mediated cleavage of APPand/or release of A beta from the substrate, the compounds of theinvention are effective to reduce beta-secretase-mediated cleavage ofAPP at the beta-secretase cleavage site and/or effective to reducereleased amounts of A beta. Where such contacting is the administrationof the inhibitory compounds of the invention to an animal model, forexample, as described above, the compounds are effective to reduce Abeta deposition in brain tissues of the animal, and to reduce the numberand/or size of beta amyloid plaques. Where such administration is to ahuman subject, the compounds are effective to inhibit or slow theprogression of disease characterized by enhanced amounts of A beta, toslow the progression of AD in the, and/or to prevent onset ordevelopment of AD in a patient at risk for the disease.

[0866] Unless defined otherwise, all scientific and technical terms usedherein have the same meaning as commonly understood by one of skill inthe art to which this invention belongs. All patents and publicationsreferred to herein are hereby incorporated by reference for allpurposes.

[0867] Definitions

[0868] The definitions and explanations below are for the terms as usedthroughout this entire document including both the specification and theclaims.

[0869] It should be noted that, as used in this specification and theappended claims, the singular forms “a,” “an,” and “the” include pluralreferents unless the content clearly dictates otherwise. Thus, forexample, reference to a composition containing “a compound” includes amixture of two or more compounds. It should also be noted that the term“or” is generally employed in its sense including “and/or” unless thecontent clearly dictates otherwise.

[0870] The symbol “—” in general represents a bond between two atoms inthe chain. Thus CH₃—O—CH₂—CH(R_(i))—CH₃ represents a2-substituted-1-methoxypropane compound. In addition, the symbol “—”represents the point of attachment of the substituent to a compound.Thus for example aryl(C₁-C₆)alkyl- indicates an alkylaryl group, such asbenzyl, attached to the compound at the alkyl moiety.

[0871] Where multiple substituents are indicated as being attached to astructure, it is to be understood that the substituents can be the sameor different. Thus for example “R_(m) optionally substituted with 1, 2or 3 R_(q) groups” indicates that R_(m) is substituted with 1, 2, or 3R_(q) groups where the R_(q) groups can be the same or different.

[0872] APP, amyloid precursor protein, is defined as any APPpolypeptide, including APP variants, mutations, and isoforms, forexample, as disclosed in U.S. Pat. No. 5,766,846.

[0873] A beta, amyloid beta peptide, is defined as any peptide resultingfrom beta-secretase mediated cleavage of APP, including peptides of 39,40, 41, 42, and 43 amino acids, and extending from the beta-secretasecleavage site to amino acids 39, 40, 41, 42, or 43.

[0874] Beta-secretase (BACE1, Asp2, Memapsin 2) is an aspartyl proteasethat mediates cleavage of APP at the amino-terminal edge of A beta.Human beta-secretase is described, for example, in WO00/17369.

[0875] Pharmaceutically acceptable refers to those properties and/orsubstances that are acceptable to the patient from apharmacological/toxicological point of view and to the manufacturingpharmaceutical chemist from a physical/chemical point of view regardingcomposition, formulation, stability and patient acceptance.

[0876] A therapeutically effective amount is defined as an amounteffective to reduce or lessen at least one symptom of the disease beingtreated or to reduce or delay onset of one or more clinical markers orsymptoms of the disease.

[0877] By “alkyl” and “C₁-C₆ alkyl” in the present invention is meantstraight or branched chain alkyl groups having 1-6 carbon atoms, suchas, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl,pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and3-methylpentyl. It is understood that in cases where an alkyl chain of asubstituent (e.g. of an alkyl, alkoxy or alkenyl group) is shorter orlonger than 6 carbons, it will be so indicated in the second “C” as, forexample, “C₁-C₁₀” indicates a maximum of 10 carbons.

[0878] By “alkoxy” and “C₁-C₆ alkoxy” in the present invention is meantstraight or branched chain alkyl groups having 1-6 carbon atoms,attached through at least one divalent oxygen atom, such as, forexample, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy,tert-butoxy, pentoxy, isopentoxy, neopentoxy, hexoxy, and3-methylpentoxy.

[0879] By the term “halogen” in the present invention is meant fluorine,bromine, chlorine, and iodine.

[0880] “Alkenyl” and “C₂-C₆ alkenyl” means straight and branchedhydrocarbon radicals having from 2 to 6 carbon atoms and from one tothree double bonds and includes, for example, ethenyl, propenyl,1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl and the like.

[0881] “Alkynyl” and “C₂-C₆ alkynyl” means straight and branchedhydrocarbon radicals having from 2 to 6 carbon atoms and one or twotriple bonds and includes ethynyl, propynyl, butynyl, pentyn-2-yl andthe like.

[0882] As used herein, the term “cycloalkyl” refers to saturatedcarbocyclic radicals having three to twelve carbon atoms. The cycloalkylcan be monocyclic, or a polycyclic fused system. Examples of suchradicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andcycloheptyl. The cycloalkyl groups herein are unsubstituted or, asspecified, substituted in one or more substitutable positions withvarious groups. For example, such cycloalkyl groups may be optionallysubstituted with C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy, cyano,nitro, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl,C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl,mono(C₁-C₆)alkylamino(C₁-C₆)alkyl or di(C₁-C₆)alkylamino(C₁-C₆)alkyl.

[0883] By “aryl” is meant an aromatic carbocyclic group having a singlering (e.g., phenyl), multiple rings (e.g., biphenyl), or multiplecondensed rings in which at least one is aromatic, (e.g.,1,2,3,4-tetrahydronaphthyl, naphthyl), which is optionally mono-, di-,or trisubstituted. Preferred aryl groups of the present invention arephenyl, 1-naphthyl, 2-naphthyl, indanyl, indenyl, dihydronaphthyl,tetralinyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl. The arylgroups herein are unsubstituted or, as specified, substituted in one ormore substitutable positions with various groups. For example, such arylgroups may be optionally substituted with, for example, C₁-C₆ alkyl,C₁-C₆ alkoxy, halogen, hydroxy, cyano, nitro, amino,mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino (C₁-C₆)alkyl, di(C₁-C₆)alkylamino(C₁-C₆)alkyl, —COOH,—C(═O)O(C₁-C₆ alkyl), —C(═O)NH₂, —C(═O)N(mono- or di-C₁-C₆ alkyl),—S(C₁-C₆ alkyl), —SO₂(C₁-C₆ alkyl), —O—C(═O) (C₁-C₆ alkyl),—NH—C(═O)—(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)-C(═O)—(C₁-C₆ alkyl),—NH—SO₂—(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)-SO₂—(C₁-C₆ alkyl), —NH—C(═O)NH₂,—NH—C(═O)N(mono- or di-C₁-C₆ alkyl), —NH(C₁-C₆ alkyl)-C(═O)—NH₂ or—NH(C₁-C₆ alkyl)-C(═O)—N-(mono- or di-C₁-C₆ alkyl).

[0884] By “heteroaryl” is meant one or more aromatic ring systems of 5-,6-, or 7-membered rings which includes fused ring systems of 9-11 atomscontaining at least one and up to four heteroatoms selected fromnitrogen, oxygen, or sulfur. Preferred heteroaryl groups of the presentinvention include pyridinyl, pyrimidinyl, quinolinyl, benzothienyl,indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl,quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl,pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl,benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl,thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl,isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl,isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl,isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl,benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl,benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl,phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl,imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl,dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl,isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide,tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl,dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl,isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide,pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinylN-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide,quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide,imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolylN-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide,benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide,thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide,benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide. The heteroarylgroups herein are unsubstituted or, as specified, substituted in one ormore substitutable positions with various groups. For example, suchheteroaryl groups may be optionally substituted with C₁-C₆ alkyl, C₁-C₆alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl ordi(C₁-C₆)alkylamino(C₁-C₆)alkyl, —COOH, —C(═O)O(C₁-C₆ alkyl), —C(═O)NH₂,—C(═O)N(mono- or di-C₁-C₆ alkyl), —S(C₁-C₆ alkyl), —SO₂(C₁-C₆ alkyl),—O—C(═O) (C₁-C₆ alkyl), —NH—C(═O)—(C₁-C₆ alkyl), —N(C₁-C₆alkyl)-C(═O)—(C₁-C₆ alkyl), —NH—SO₂—(C₁-C₆ alkyl), —N(C₁-C₆alkyl)-SO₂—(C₁-C₆ alkyl), —NH—C(═O)NH₂, —NH—C(═O)N(mono- or di-C₁-C₆alkyl), —NH(C₁-C₆ alkyl)-C(═O)—NH₂ or —NH(C₁-C₆ alkyl)-C(═O)—N-(mono- ordi-C₁-C₆ alkyl).

[0885] By “heterocycle”, “heterocycloalkyl” or “heterocyclyl” is meantone or more carbocyclic ring systems of 3-, 4-, 5-, 6-, or 7-memberedrings which includes fused ring systems of 9-11 atoms containing atleast one and up to four heteroatoms selected from nitrogen, oxygen, orsulfur. Preferred heterocycles of the present invention includemorpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinylS,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl,tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl,homopiperidinyl, homomorpholinyl, homothiomorpholinyl,homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl,dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl,dihydrofuryl, dihydropyranyl, azepanyl, diazepanyl, tetrahydrothienylS-oxide, tetrahydrothienyl S,S-dioxide and homothiomorpholinyl S-oxide.The heterocycle groups herein maybe unsubstituted or, as specified,substituted in one or more substitutable positions with various groups.For example, such heterocycle groups may be optionally substituted withC₁-C₆ alkyl, C₁-C₆ alkoxy, halogen, hydroxy, cyano, nitro, amino,mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl,mono(C₁-C₆)alkylamino(C₁-C₆)alkyl, di(C₁-C₆)alkylamino(C₁-C₆)alkyl or═O.

[0886] All patents and publications referred to herein are herebyincorporated by reference for all purposes.

[0887] Structures were named using Name Pro IUPAC Naming Software,version 5.09, available from Advanced Chemical Development, Inc., 90Adelaide Street West, Toronto, Ontario, M5H 3V9, Canada.

[0888] The present invention may be better understood with reference tothe following examples. These examples are intended to be representativeof specific embodiments of the invention, and are not intended aslimiting the scope of the invention.

CHEMISTRY EXAMPLES

[0889] The following detailed examples describe how to prepare thevarious compounds and/or perform the various processes of the inventionand are to be construed as merely illustrative, and not limitations ofthe preceding disclosure in any way whatsoever. Those skilled in the artwill promptly recognize appropriate variations from the procedures bothas to reactants and as to reaction conditions and techniques.

[0890] Preparation 1 tert-Butyl(1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate (III)

[0891] N-methyl-morpholine (5.83 Ml, 53 mmole, 1.05 eq.) is added to(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid(II, 15 g, 50 mmole) in THF (100 mL) and the reaction is cooled to −78°.Isobutyl chloroformate (6.87 mL, 53 mmole, 1.05 eq.) is added rapidly.The cold bath is then removed and the mixture stirred for 1 hr. Thereaction was monitored by TLC to insure completion of the reaction andthe mixture is then filtered and washed with dry THF (50 ml) and keptcold in the filtered flask at −20°.

[0892] In a ice-salt bath is placed a 500 ml graduate cylindercontaining ether (200 mL) and aqueous potassium hydroxide (40%, 60 ml).1-methyl-3-nitro-1-nitrosoguanidine (5.6 g, 106 mmole, 2.1 eq.) is addedslowly with stirring and temperature kept below zero degree. The mixtureturned yellow and the bubbling lasted for 10 minutes. The stirring isstopped and without mixing the layers, the top diazomethane ethereallayer is transferred with non-ground tip pipette into the stirred mixedanhydride mixture at −20°. The reaction is monitored by TLC (ethylacetate/hexane, 50/50; R_(f)=0.69). After 1 hour nitrogen is thenbubbled into the mixture. The solvent is removed under reduced pressure(with heat) and the mixture is partitioned between ether and water. Thephases are separated, the organic phase is washed with bicarbonate,saline, dried over anhydrous sodium sulfate, filtered, and solventremoved under reduced pressure (with heat). The residue is dissolved inether (100 mL) and hydrobromous acid (48%, 15 mL, 135 mmole, 2.7 eq,) isadded at −20°, the cold bath is removed and the mixture is stirred foranother half hour. The reaction is monitored by TLC (ethylacetate/hexane, 50/50; R_(f)=0.88). The mixture is partitioned betweenether and water, washed with bicarbonate, saline, dried over anhydroussodium sulfate, filtered, and the solvent removed. The residue isrecrystallized from ethanol to give the title compound, TLC (ethylacetate/hexane, 50/50) R_(f)=0.88; MS (MH⁺)=379.3

[0893] Preparation 2 tert-Butyl (1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV)

[0894] Sodium borohydride (1.32 g, 34.9 mmole, 1.1 eq.) is added totert-Butyl (1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate(III, PREPARATION 1, 12 g, 31.75 mmole) dissolved in absolute alcohol(500 mL) −78°. The reaction mixture is stirred for 30 minutes andmonitored by TLC (ethyl acetate/hexane, 20/80; R_(f)=0.2). The mixtureis quenched with water (10 mL) and the solvent removed under reducedpressure with heat (not exceeding 300) to dryness. The solid ispartitioned between dichloromethane and water, washed with saline, driedover anhydrous sodium sulfate. The solvent is removed under reducedpressure to give the title compound, TLC (ethyl acetate/hexane, 20/80)R_(f)=0.2; MS (MH⁺)=381.2

[0895] Preparation 3 tert-Butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V)

[0896] tert-Butyl (1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV,PREPARATION 2) is dissolved in absolute alcohol (150 mL) and ethylacetate (100 mL) and potassium hydroxide (2.3 g, 34.9 mmole, 1.1 eq.) inethyl alcohol (85%, 5 mL) is added at −20°. The cold bath is thenremoved and the mixture stirred for 30 minutes. The reaction ismonitored by TLC (ethyl acetate/hexane, 20/80). When the reaction iscomplete, it is diluted with dichloromethane and extracted, washed withwater, saline, dried over anhydrous sodium sulfate and the solventremoved under reduced pressure. The crude material is purified by flashchromatography on silica gel to give the title compound, TLC (ethylacetate/hexane, 20/80) R_(f)=0.3; MS (MH⁺)=300.4.

[0897] Preparation 4: tert-Butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-(triflurormethyl)benzyl)amino]-propylcarbamate

[0898] tert-Butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (PREPARATION3, 8.5 g, 28.4 mmole) is mixed with isopropanol (145 ml). The reactionflask is charged with 3-(trifluoromethyl)benzylamine. The reactionmixture is heated to reflux for 3 hours, HPLC analysis indicatescomplete disappearance of the epoxide. The reaction mixture isconcentrated under reduced pressure and the residue is partitionedbetween ethyl acetate and aqueous hydrochloric acid. The organic phaseis separated and washed with aqueous hydrochloric acid, bicarbonate, andsaline then dried over sodium sulfate. Concentration under reducedpressure and recrystallization from hot hexane gives the title compound,MS (MH⁺) 475.

[0899] Preparation 5: tert-Butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{(tert-butyloxy)carbonyl-3-{(trifluoromethyl)benzyl}amino}propylcarbamate

[0900] To a solution of tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-(triflurormethyl)benzyl)-amino]propylcarbamate(PREPARATION 4, 6.2 g, 13.1 mmole) in THF (70 ml) at 0° is addeddi-tert-butyl pyrocarbonate (6.3 g, 28.9 mmole). The reaction mixture isstirred at 20-25° for 18 hours. The reaction mixture is diluted withdiethyl ether and washed with bicarbonate, 0.5 M citric acid, and salinethen dried over sodium sulfate and concentrated to give the titlecompound, MS (MNa⁺) 597.

[0901] Preparation 6: 3-iodo-5-(methoxycarbonyl)benzoic acid

[0902] To an ice-cold, stirred solution of commercially available3-amino-5-(methoxycarbonyl)benzoic acid (5.19 g, 26.59 mmol) in 2 Nhydrochloric acid (156 mL) was added a solution of sodium nitrite (1.84g, 26.67 mmol) in water (10.8 mL). This mixture was then added dropwiseto an ice-cold, stirred solution of potassium iodide (8.84 g, 53.25mmol) in water (26.2 mL). After stirring for 35 min, the reactionmixture was diluted with water and extracted with ethyl acetate. Theorganic layer was washed with 5% aqueous sodium thiosulfate, andsaturated sodium chloride, dried (sodium sulfate), and concentratedunder reduced pressure. Purification by flash column chromatography(silica, 50:50:2 hexanes/ethyl acetate/acetic acid) afforded the titlecompound (4.48 g, 55% yield) as an off-white solid. ESI-MS (m/z): 305[M+H]⁺.

[0903] Preparation 7:3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoic acid

[0904] To a −70° C. solution of oxazole (4.0 g, 58 mmol) intetrahydrofuran (100 mL) was added n-butyllithium (1.6 M in hexanes, 40mL, 64 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 166 mL,166 mmol) was added and the reaction mixture was warmed to 0° C. for 1h. To this mixture was added 3-iodo-5-(methoxycarbonyl)benzoic acid(PREPARATION 6, 21.4 g, 55 mmol) and palladium(0)tetrakis(triphenylphosphine) (2.7 g, 2.34 mmol). The reaction mixturewas heated at reflux for 1 h. The reaction mixture was diluted withethyl acetate (300 mL), washed with water, and saturated sodiumchloride. The organic layer was dried (sodium sulfate) and concentratedunder reduced pressure. Purification by silica gel plug (10-33% ethylacetate/hexanes) provided an oxazole (17.7 g, 97%) as a light yellowsolid: ¹H NMR (300 MHz, CDCl₃) δ 8.73 (t, J=2 Hz, 1H), 8.24 (t, J=2 Hz,1H), 8.11 (t, J=2 Hz, 1H), 7.77 (d, J=1 Hz, 1H), 7.28 (d, J=1 Hz, 1H),3.97 (s, 3H), 3.49 (m, 2H), 3.19 (m, 2H), 1.71 (m, 2H), 1.57 (m, 2H),1.01 (m, 3H), 0.76 (m, 3H).

[0905] To a stirred solution of the ester from step 1 (17.7 g, 53.6mmol) in tetrahydrofuran (50 mL), methanol (25 mL), and water (25 mL)was added lithium hydroxide monohydrate (6.92 g, 165 mmol). The reactionmixture was stirred at room temperature for 2 h, and then concentratedunder reduced pressure. The residue was partitioned between water (100mL) and diethyl ether (100 mL). The aqueous layer was acidified to pH4-5 with hydrochloric acid and extracted with ethyl acetate (3×200 mL).The combined organic layers were washed with saturated sodium chloride,dried (sodium sulfate), and concentrated under reduced pressure toone-half its original volume. The resulting precipitate was collected byfiltration and washed with hexanes to provide the title compound (15.5g, 91%) as an off-white solid: mp 131-133° C.; ¹H NMR (300 MHz, CD₃OD) δ8.72 (s, 1H), 8.22 (s, 1H), 8.10 (s, 1H), 8.06 (d, J=1 Hz, 1H), 7.36 (d,J=1 Hz, 1H), 3.52 (m, 2H), 3.25 (m, 2H), 1.76 (m, 2H), 1.62 (m, 2H),1.02 (m, 3H), 0.76 (m, 3H); APCI MS m/z 317 [M+H]⁺.

[0906] Preparation 8:(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochloride

[0907] To a solution of tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{(tert-butyloxy)carbonyl-3-{(trifluoromethyl)benzyl}amino}propylcarbamate(PREPARATION 5, 594 mg, 1.0 mmole) in DMF (2 mL) is added3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoic acid (PREPARATION7, 316 mg, 1.0 mmole), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (210 mg, 1.1 mmole), and 4-(dimethylamino)pyridine (146mg, 1.2 mmole). After ˜36 hours, the reaction mixture is diluted withethyl acetate and washed with bicarbonate (2×) and brine (4×) then driedover sodium sulfate, filtered, and concentrated under reduced pressure.The concentrate is purified on silica gel by flash chromatography usinga gradient solvent of ethyl acetate/hexane (20/80 to 50/50) to give(1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-({(tert-butoxycarbonyl)[3-(trifluoromethyl)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate, MS (MNa⁺) 895.

[0908](1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-({(tert-butoxycarbonyl)[3-(trifluoromethyl)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate (482 mg, 0.55mmole) is dissolved in hydrochloric acid/dioxane (4N, 3 ml) is stirredfor 1 hour at 20-25°. The solvent is then removed under reduced pressureto give the title compound, MS (MH⁺) 673.

[0909] Preparation 9:N˜1˜-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N˜3˜,N˜3˜-dipropyl-N˜1˜-[3-(trifluoromethyl)benzyl]isophthalamidehydrochloride

[0910] To a solution of tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-(trifluorormethyl)benzyl)amino]propylcarbamate(PREPARATION 4, 393 mg, 0.83 mmole) in DMF (2 mL) is added3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoic acid (PREPARATION7, 262 mg, 0.83 mmole), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (175 mg, 0.91 mmole), and 4-(dimethylamino)pyridine (122mg, 1.0 mmole). After ˜18 hours, the reaction mixture is diluted withethyl acetate and washed with bicarbonate (2×) and brine (4×) then driedover sodium sulfate, filtered, and concentrated under reduced pressure.The concentrate is purified on silica gel by flash chromatography usinga gradient solvent of ethyl acetate/hexane (50/50 to 70/30) to givetert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoyl][3-(trifluoromethyl)benzyl]amino}-2-hydroxypropylcarbamate,MS (MH⁺) 773.

[0911] tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoyl][3-(trifluoromethyl)benzyl]amino}-2-hydroxypropylcarbamate(226 mg, 0.29 mmole) is dissolved in hydrochloric acid/dioxane (4N, 2ml) is stirred for 20 minutes at 20-25°. The solvent is then removedunder reduced pressure and the crude material purified by reverse phaseHPLC using a gradient aolvent of acetonitrile/water with 0.5%trifluoroacetic acid. The trifluoroacetic acid salt obtained isconverted to the hydrochloric salt by treatment with HCl in methanol(1.25 M, 5 mL). Concentration under reduced pressure gives the titlecompound, MS (MH⁺) 673.

[0912] The following compounds are prepared essentially according to theprocedures described in the schemes, charts, examples and preparationsset forth herein. Comp [M + # Structure Compound Name(s) H]+ 9

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N¹-(3- ethylbenzyl)-D-alaninamide dihydrochloride 526 10

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N¹-(3-ethylbenzyl)- N²[(benzyloxy)carbonyl]-3- [(1-propylbutyl)sulfonyl]-D-alaninamide trifluoroacetate 702 11

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1- propylbutyl)sulfonyl]-D- alaninamide hydrochloride568 12

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-2- [(methylsulfonyl)amino]-1,3- thiazole-5-carboxamide 53913

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1- propylbutyl)sulfonyl]-L- alaninamidebis(trifluoroacetate) 568 14

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N-(3- ethylbenzyl)propanamide hydrochloride 511 15

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1- ethylbenzyl)amino]methyl}propyl 3- (butylsulfonyl)propanoate dihydrochloride 511 16

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}p ropyl 3- [(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochloride 633 17

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]ami no}methyl)propyl 3-[(dipropylamino)carbonyl]- 5-(1,3-oxazol-2-yl)benzoate dihydrochloride659 18

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amin o}methyl)propyl 3-[(dipropylamino)carbonyl]- 5-( 1,3-oxazol-2-yl)benzoate dihydrochloride673 19

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N\(u)1\(d)-(3- ethylbenzyl)-5-(1,3-oxazol- 2-yl)-N³,N³-dipropylisophthalamide hydrochloride 633 20

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol- 2-yl)-N³,N³-dipropyl-N¹-[3-(trifluoromethyl)benzyl]isop hthalamide hydrochloride 673 21

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol- 2-yl)-N³,N³-dipropyl-N¹-[3-(trifluoromethyl)benzyl]isop hthalamide 673 22

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]a mino}methyl)propyl 3-[(dipropylamino)carbonyl]- 5-(1,3-oxazol-2-yl)benzoate 655 23

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N¹-(3- ethylbenzyl)- N²[(methoxy)carbonyl]-D-alaninamide dihydrochloride 584 24(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(2-hydroxyethyl)amino]sulfonyl}benzoate 26(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 28(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-isopropylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 30 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-isopropylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate 32 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzoate 34(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-(4-methyl-1,3- oxazol-2-yl)benzoate 36(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2- yl)benzoate 38 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(3-hydroxypropyl)amino]sulfonyl}benzoate hydrochloride 40(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-propylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 42 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(methyl)amino]carbonyl}-5-methylbenzoate 44 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 46(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(3-isobutylisoxazol-5-yl)methyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 48

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dimethylamino)sulfonyl]-5-[(dipropyl amino)carbonyl]benzoate 50

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropyl amino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate hydrochloride 52

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-({[3-(5-formyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 54

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 3-bromo-5-[(dipropyl-amino)carbonyl]benzoate 56

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[93-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[(1R)-2- hydroxy-1-methylethyl]amino}sulfonyl)benzoate 58

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-isobutylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 60

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 62(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzoate hydrochloride 64(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[(1S)-2-hydroxy-1-methylethyl]amino}sulfonyl)benzoate 66(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(propyl)amino]carbonyl}-5-methylbenzoate 68 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dibutylamino)carbonyl]-5-methylbenzoate 70(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-hydroxyprop-1-yn-1-yl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 72(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl}benzoate 74(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(ethyl)amino]carbonyl}-5-methylbenzoate 76 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate 78 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[cyclohexyl(methyl)amino]carbonyl}-5-methylbenzoate 80(1R,2S)-2-amino-1-({[3-(cyclopropylamino)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 82(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3- thienyl)benzyl]amino)methyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate 84(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino) methyl)propyl3-[(dipropylamino)carbonyl]-5- (1,3-oxazol-2-yl)benzoate 86(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-(piperazin-1- ylsulfonyl)benzoatedihydrochioride 88 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-iodophenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 90(1R,2S)-2-amino-1-{[(3-sec-butylbenzyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 92(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(3-methylisoxazol-4-yl)benzoate hydrochloride 94(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylaniino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate 96(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5- (1,3-oxazol-2-yl)benzoate 98(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[(dipropylamino)carbonyl]-6-methylisonicotinate 100 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(cyclopropylmethyl)(propyl)amino]carbonyl}-5-methylbenzoate 102(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate 104(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]- 5-(1,3-oxazol-2-yl)benzoate 106(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(aminosulfonyl)-5-[(dipropylamino)carbonyl]benzoate 108(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(1Z)-prop-1-en-1-yl]benzyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 110(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-(1H-pyrazol- 4-yl)benzoate hydrochloride112 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 114 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 116(1R,2S)-1-{[(3-allylbenzyl)amino]methyl}-2-amino-3-(3,5-difluorophenyl)propyl 3-[dipropylamino)carbonyl]-5-methylbenzoate 118(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 120(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methylethyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2- yl)benzoate 122(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[ethyl(propyl)amino]carbonyl}-5-methylbenzoate 124(1R,2S)-2-amino-1-({[3-(cyclopropylamino)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 126(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]- 5-ethynylbenzoate 128(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 130(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(5-formyl-4-methyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 132 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-isopropylbenzyl)amino]methyl}propyl5-[(dipropylamino)carbonyl]nicotinate 134(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(methylsulfonyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 136(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(butylamino)carbonyl]-5-methylbenzoate 138(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-methylbutyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 140(1R,2S)-2-amino-1-{[(biphenyl-3-ylmethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 142(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]- 5-methylbenzoate 144(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[2-(methylamino)ethyl]amino}sulfonyl)benzoate hydrochloride 146(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate 148

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diallylamino)carbonyl]-5-methylbenzoate 150

(1R,2R)-2-amino-3- (3,5-difluorophenyl)-1-({[1-(2-isobutyl-1,3-thiazol-5- yl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino) carbonyl]-5-methylbenzoate 152

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methyl- ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 154

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2-hydroxyethyl) amino]sulfonyl}-5-[(propylamino) carbonyl]benzoate 156

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(propyl)amino]carbonyl}benzoate 158

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 160

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diethylamino)carbonyl]-5-(1,3-oxazol-2- yl)benzoate 162

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzylamino)carbonyl]-3-[(1-propylbutyl) sulfonyl]alaninate trifluoroacetate 164

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-pyridin-3-ylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methyl benzoate 166(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(dipropylamino)carbonyl]nicotinate 1-oxide 168 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-forrnyl-2-furyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 170 (1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-(1-methyl-1H- imidazol-2-yl)benzoate 172(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(diethylamino)carbonyl]-5-methylbenzoate 174(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(ethylsulfinyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 176 (1R,2S)-2-amino-3-(3,5-difluorophenyly-1-{[(3-ethylbenzyl)amino]methyl}propyl3-{[butyl(ethyl)amino]sulfonyl}propanoate 178(1R,2S)-2-amino-1-{[(3-cyanobenzyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 180(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]propanoatehydrochloride 182 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[isobutyl(methyl)amino]carbonyl}-5-methylbenzoate 184

186

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-pyridin-2-ylbenzyl)amino]methyl}propyl 3-[(dipropyl amino)carbonyl]-5-methylbenzoate 188

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 2-[(methylsulfonyl) amino]-1,3-oxazole-4-carboxylate 190

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-[({3- [methyl(methylsulfonyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino) carbonyl]-5-methylbenzoate 192

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninate trifluoroacetate 194(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(ethylsulfonyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 196 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-chloro-2-thienyl)sulfonyl]-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 198(1R,2S)-1-({[3-(5-acetyl-2-thienyl)benzyl]amino}methyl)-2-amino-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 200(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(sec-butylamino)carbonyl]-5-methylbenzoate 202 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1,3-oxazol-2-yl)benzoatehydrochloride 204 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(2-phenylethyl)amino]carbonyl}benzoate 206(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3,5-dimethylisoxazol-4-yl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 208(1R,2SJ-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(prop-2-yn-1-yl)amino]carbonyl}benzoate 210(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[ethyl(methyl)amino]carbonyl}-5-methylbenzoate 212 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-{[(dimethylamino)carbonyl]oxy}benzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5 -methylbenzoate 214(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[benzyl(methyl)amino]carbonyl}-5-methylbenzoate 216 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[sec-butyl(propyl)amino]carbonyl}-5-methylbenzoate 218(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(4-methyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 220 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(methoxycarbonyl)(methyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 222(1R,25)-2-amino-1-({[3-(trifluoromethyl)benzyl]amino}methyl)-3-(2,3,5-trifluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 224(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diisobutylamino)carbonyl]-5-methylbenzoate 226 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(2-pyridin-2-ylethyl)amino]carbonyl}benzoate 228(1R,2S)-2-amino-3-(3-fluoro-5-hydroxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate hydrochloride 230(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 232(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzoate 234 (1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-D-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 236

238

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-{[(3-pyridin-4-ylbenzyl)amino]methyl}propyl 3-[(dipropyl amino)carbonyl]-5-methylbenzoate 240

(1R,2S)-2-amino-3- (3,5-difluorophenyl)-1-[({3-[(dimethylamino)sulfonyl]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 242(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 244(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate 246(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(azepan-1-ylcarbonyl)-5-methylbenzoate248 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(methoxycarbonyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 250(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-L-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 252(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(isobutylamino)carbonyl]-5-methylbenzoate 254 4-[((1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl)oxy]-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoic acid trifluoroacetate 256(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[methyl(methylsulfonyl)amino]benzoate25N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl-N-(3-ethylbenzyl)-5-{[(2-hydroxyethyl)amino]sulfonyl}-N′,N′-dipropylisophthalamide 27N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[(2-isobutyl-1,3-thiazol-5-yl)methyl]-N′,N′-dipropylisophthalamide 29N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-(3-isopropylbenzyl)-N′,N′-dipropylisophthalamide 31N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isopropylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 33N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfony}-N′,N′-dipropylisophthalamide 35N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(4-methyl-1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 37N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2-isobutyl-1,3-thiazol-5-yl)methyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 39N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)5-{[(3-hydroxypropyl)amino]sulfonyl}-N′,N′-dipropylisophthalamidehydrochloride 41N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3-propylbenzyl)isophthalamide 43N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-N′,5-dimethylisophthalamide 45N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-(3-ethynylbenzyl)-N′,N′-dipropylisophthalamide 47N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[(3-isobutylisoxazol-5-yl)methyl]-N′,N′-dipropylisophthalamide 49N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-[(dimethylamino)sulfonyl]-N-(3-ethylbenzyl)-N′,N′-dipropylisophthalamide51N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide hydrochloride 53N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(5-formyl-2-thienyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 55N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-bromo-N-(3-iodobenzyl)-N′,N′-dipropylisophthalamide 57N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[(1R)-2-hydroxy-1-methylethyl]amino}sulfonyl)-N′,N′-dipropylisophthalamide 59N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isobutylbenzyl)-5-methyl-N′,N′-dipropylisophthalamide 61N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamide 63N-[(2R,3.S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzamidehydrochloride 65N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[(1S)-2-hydroxy-1-methylethyl]amino}sulfonyl)-N′,N′-dipropylisophthalamide 67N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide 69N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-dibutyl-N-(3-ethylbenzyl)-5-methylisophthalamide 71N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(3-hydroxyprop-1-yn-1-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 73N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)5-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl}-N′,N′-diproplisophthalamide 75N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamide 77N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3 -ethynylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 79N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-cyclohexyl-N-(3-ethylbenzyl)-N′,5-dimethylisophthalamide 81N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(cyclopropylamino)benzyl]-5-ethynyl-N′,N′-dipropylisophthalamide 83N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-[3-(3-thienyl)benzyl]isophthalamide 85N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropyl-N-[3-trifluoromethyl)benzyl]isophthalamide 87N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(piperazin-1-ylsulfonyl)-N′,N′-dipropylisophthalamide dihydrochloride89 N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-iodophenyl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamide 91N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3 -sec-butylbenzyl)-5-methyl-N′,N′-dipropylisophthalamide 93N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(3-methylisoxazol-4-yl)-N′,N′-dipropylisophthalamide hydrochloride 95N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-isobutylisoxazol-5-yl)cyclopropyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 97N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)cyclopropyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide99 N⁴-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N⁴-(3-ethylbenzyl)-6-methyl-N²,N²-dipropylpyridine-2,4-dicarboxamide 101N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(cyclopropylmethyl)-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide103 N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 105

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-[1-(3-ethynylphenyl)cyclopropyl]-5- (1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide 107

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-(aminosulfonyl)-N-(3-ethylbenzyl)- N′,N′-dipropylisophthalamide 109

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3-[(1Z)-prop-1-en-1-yl]benzyl}-N′,N′-dipropylisophthalamide111

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-dipropyl-5- (1H-pyrazol-4-yl)isophthalamidedihydrochloride 113

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-ethynyl-N′,N′dipropylisophthalamide 115

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-[3- (trifluoromethyl)benzyl]isophthalamide 117

N-(3-allylbenzyl)-N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamide 119

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-[1-(3-ethylphenyl)cyclopropyl]-5 -methyl-N′,N′- dipropylisophthalamide 121N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide123N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide 125N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(cyclopropylamino)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 127N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[1-(3-ethynylphenyl)cyclopropyl]-N′,N′-dipropylisophthalamide 129N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-isobutylisoxazol-5-yl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamide131N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(5-formyl-4-methyl-2-thienyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 133N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isopropylbenzyl)-N′,N′-dipropylpyridine-3,5-dicarboxamide 135N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3-[(methylsulfonyl)amino]benzyl}-N′,N′-dipropylisophthalamide 137N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-5-methylisophthalamide 139N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(3-methylbutyl)benzyl]-N′,N′-dipropylisophthalamide 141N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(biphenyl-3-ylmethyl)-5-methyl-N′,N′-dipropylisophthalamide 143N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethynylphenyl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamide 145N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[2-(methylamino)ethyl]amino}sulfonyl)-N′,N′-dipropylisophthalamidehydrochloride 147N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[1-(3-isobutylisoxazol-5-yl)cyclopropyl]-N′,N′-dipropylisophthalamide 149N,N-diallyl-N′-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3-ethylbenzyl)-5-methylisophthalamide 151N-[(2R,3R)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(2-isobutyl-1,3-thiazol-5-yI)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamide 153N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamide 155N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(2-hydroxyethyl)amino]sulfonyl}-N′-propylisophthalamide 157N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzylyN′,5-dimethyl-N′-propylisophthalamide 159N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninamidehydrochloride 161N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-diethyl-N-(3-ethylbenzyl)-5-(1,3 oxazol-2-yl)isophthalamide 163N¹-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-[(benzylamino)carbonyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide trifluoroacetate (salt) 165N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3-pyridin-3 -ylbenzyl)isophthalamide 167N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-dipropylpyridine-3,5-dicarboxamide 1-oxide 169N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-[3-(3-formyl-2-furyl)benzyl]-5-methyl-N′-propylisophthalamide 171N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1-methyl-1H-imidazol-2-yl)-N′,N′-dipropylisophthalamide 173N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-diethyl-N-(3-ethylbenzyl)-5-methylisophthalamide 175N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(ethylsulfinyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 177N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-{[butyl(ethyl)amino]sulfonyl}-N-(3-ethylbenzyl)propanamide 179N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-cyanobenzyl)-5-methyl-N′,N′-dipropylisophthalamide 181N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]propanamide hydrochloride 183N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isobutyl-N′,5-dimethylisophthalamide 185

187

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-methyl-N′,N′- dipropyl-N-(3-pyridin-2- ylbenzyl)isophthalamide 189

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-iodobenzyl)-2-[(methyl sulfonyl)amino]-1,3-oxazole- 4-carboxamide 191

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-methyl-N-{3-[methyl(methyl sulfonyl)amino]benzyl}-N′,N′-dipropylisophthalamide193

N¹-[(2R,3S)-3- amino-4-(3,5-difluorophenyl) -2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(3-phenylpropanoyl) -3-[(1-propylbutyl)sulfonyl]alaninamidetrifluoroacetate (salt) 195

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-[3-(ethylsulfonyl)benzyl]-5-methyl- N′,N′-dipropylisophthalamide 197

N¹-[(2R,3S)-3- amino-4-(3,5 -difluoro phenyl)-2-hydroxybutyl]-N²-[(5-chloro-2- thienyl)sulfonyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl) sulfonyl]alaninamide hydrochloride 199N-[3-(5-acetyl-2-thienyl)benzyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamide 201N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(sec-butyl)-N-(3-ethylbenzyl)-5-methylisophthalamide 203N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1,3-oxazol-2-yl)benzamide hydrochloride 205N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-(2-phenylethyl)isophthalamide 207N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(3,5-dimethylisoxazol-4-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 209N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-prop-2-yn-1-ylisophthalamide 211N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-N′,5-dimethylisophthalamide 2133-[([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)methyl]phenyldimethylcarbamate 215N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-benzyl-N-(3-ethylbenzyl)-N40 ,5-dimethylisophthalamide 217N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(sec-butyl)-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide 219N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(4-methyl-2-thienyl)benzyl]-N′,N′-dipropylisophthalamide 221 methyl{3-[([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)methyl]phenyl}methylcarbamate 223N-[(2R,3S)-3-amino-2-hydroxy-4-(2,3,5-trifluorophenyl)butyl]-5-methyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamide 225N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-diisobutyl-5-methylisophthalamide 227N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-(2-pyridin-2-ylethyl)isophthalamide 229N-[(2R,3S)-3-amino-4-(3-fluoro-5-hydroxyphenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide hydrochloride 231N¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 233N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-hydroxy-N-(3-iodobenzyl)-3-(pyrrolidin-1-ylcarbonyl)benzamide 2355-oxo-D-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochloride237

239

N-[(2R,3S)-3-amino-4-(3,5 -difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′- dipropyl-N-(3-pyridin-4-yl benzyl)isophthalamide241

N-[(2R,3S)-3-amino-4-(3,5 -difluorophenyl)-2-hydroxybutyl]-N-{3-[(dimethyl amino)sulfonyl]benzyl}-5- methyl-N′,N′-dipropylisophthalamide 243

N-[(2R,3S)-3-amino-4-(3,5 -difluorophenyl)-2-hydroxybutyl]-N-(6-methoxy-1,2,3,4- tetrahydronaphthalen-1-yl)- 5-methyl-N′,N′-dipropylisophthalamide 245N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamide247N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(azepan-1-ylcarbonyl)-N-(3-ethylbenzyl)-5-methylbenzamide 249methyl{3-[([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)methyl]phenyl}carbamate2515-oxo-L-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochloride253N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N¹-isobutyl-5-methylisophthalamide 2554-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoicacid trifluoroacetate (salt) 257N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[methyl(methylsulfonyl)amino]benzamide 258(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[ethyl(isopropyl)amino]carbonyl}-5-methylbenzoate 260(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(2-thienyl)propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate 262(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}propanoate 264(1R,2S)-2-amino-3-(3,5-difluorophenyly-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[isopropyl(methyl)amino]carbonyl}-5-methylbenzoate 266 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl2-[(methylsulfonyl)amino]-1,3-thiazole-4- carboxylate 268(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[allyl(cyclopentyl)amino]carbonyl}-5-methylbenzoate 270

272

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3-methylbutyl) sulfonyl]propanoate274

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-({[3-(5-methyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 276

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-(3-methoxyphenyl)propyl 3- (aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 278(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-methylhexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 280(1R,2S)-2-amino-1-({[1-(aminocarbonyl)cyclohexyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 282(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2E)-hex-2-en-1-ylamino]methy}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 284(1R,2S)-2-amino-3-(4-fluorophenyl)-1- methoxybenzyl)amino]methy}propyl3-[(dipropylamino)carbonyl]-5- methylbenozate 286(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-hydroxyisoxazole-5-carboxylate 288(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(1E)-hex-1-en-1-yl]benzyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 290(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(isopropylamino)carbonyl]-5-methylbenzoate 292(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(2-thienyl)propyl3- (aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 294(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [3-(2-amino-2-oxoethoxy)phenyl]acetate296 (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 298(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-ethylhexyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 300(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(6-methoxypyridin-3-yl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 302(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(2,4-dimethoxypyrimidin-5-yl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 304(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-ethylbutanoyl)benzoate 306(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzoate 308 (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 310(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-[2′-(aminocarbonyl)biphenyl-4-yl]-4-oxobutanoate 312

314

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3-hydroxypiperidin-1-yl)carbonyl]-5- methylbenzoate 316

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-hydroxy-1-phenylpropyl)amino ]methyl}propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate 318

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[[2-(dimethylamino)ethyl](ethyl)amino]carbonyl}-5-methylbenzoate 320(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxylate 322(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (5-acetyl-2-thienyl)acetate 324(1R,2S)-2-amino-3-(3,5-dichiorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 326(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diisopropylamino)carbonyl]-5-methylbenzoate 328 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(methylsulfonyl)amino]benzoate 330(1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 332(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [4-(2-oxopyrrolidin-1-yl)phenyl]acetate334 (1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate336 (1R,25)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 338

340 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}benzoate trihydrochloride 342(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-[(pentylamino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 344(1R,2S)-2-amino-3-(4-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 346(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-chloro-5-fluorophenyl)propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate 348(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[cyclohexyl(ethyl)amino]carbonyl}-5-methylbenzoate 350(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-({[(2,4-difluorophenyl)amino]carbonyl}oxy)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 352(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzoate hydrochloride 354(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 356(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 358(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,8-dimethylguinoline-3-carboxylate 360(1R,2SJ-2-amino-3-(3,5-difluorophenyl)-1-{[(6-hydroxyhexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 362 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2R)-2-hydroxypropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 364(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-[(1-propylbutyl)sulfonyl]propanoate 366(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzoate 368(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(4-phenylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 370 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl7-(1H-imidazol-1-yl)-5,6-dihydronaphthalene- 2-carboxylate 372(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(acetylamino)-4-methylbenzoate 374(1R,2S)-2-amino-1-({[2-(aminosulfonyl)ethyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 376(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-(ethylthio)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 378(1R,2S)-2-amino-3-cyclohexyl-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 380(1R,2S)-2-amino-1-{[benzyl(cyanomethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 382(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-hydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 384(1R,2S)-2-amino-1-{[(3-butoxypropyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 386(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[2-(2-hydroxyethyl)piperidin-1-yl]carbonyl}-5-methylbenzoate 388

390

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1-hydroxy-2-propyl pentyl)benzoate392

(1R,2S)-2-amino-1-[(benzylamino) methyl]-3-(3-chloro-5-fluorophenyl)propyl 3-(amino carbonyl)-5-[(dipropylamino)carbonyl]benzoate 394(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(methylsulfonyl)amino]butanoatetrifluoroacetate 396(1R,2S)-2-amino-1-({[3-(1-benzothien-2-yl)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 398(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(benzyloxy)isoxazole-5-carboxylate 400(1R,2S)-2-amino-1-{[(cyclopropylmethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl N- [(benzyloxy)carbonyl]-3- [(1-propylbutyl)sulfonyl]alaninate trifluoroacetate 402

404 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(1H-pyrazol-1-yl)pentanoate 406(1R,25)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1-(2-furylmethyl)-5-oxopyrrolidine-3-carboxylate 408(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-ethylhexanoate hydrochloride 410(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-hydroxypentyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 412 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-{[(3-methoxybenzyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]piperidine-1- carboxylate 414(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl3-[(diethylamino)carbonyl]piperidine-1- carboxylate 416(1R,2S)-2-amino-3-(pentafluorophenyl-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate 418(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(methylsulfonyl)amino]benzoate 420

422 (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate424(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(2-thienyl)propyl3- [(dipropylamino)sulfonyl]propanoate 426(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethoxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 428(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2-thienyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 430

432 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-(phenylsulfonyl)butanoatehydrochloride 434 (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 436(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 259N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-N′-isopropyl-5-methylisophthalamide 261N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyly-N-(3-methoxybenzyly)-5-methyl-N′,N′-dipropylisophthalamide 263N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}propanamide 265N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isopropyl-′,5-dimethylisophthalamide 267 N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide 269N-allyl-N′-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-cyclopentyl-N¹-(3-ethylbenzyl)-5-methylisophthalamide 271

273N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(3-methylbutyl)sulfonyl]propanamide 275N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(5-methyl-2-thienyl)benzyl]-N′,N′-dipropylisophthalamide 277N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 279N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(1-methylhexyl)-N′,N′-dipropylisophthalamide 281N-[1-(aminocarbonyl)cyclohexyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamide 283 N-[(2R,3S)-3-amino-4-(3 ,5-difluorophenyl)-2-hydroxybutyl]-N [(2E)-hex-2-en-1-yl]-5-methyl-N′,N40 -dipropylisophthalamide 285N-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 287N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-hydroxyisoxazole-5-carboxamide 289N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{3-[(1E)-hex-1-en-1-yl]benzyl}-5-methyl-N′,N′-dipropylisophthalamide 291N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isopropyl-5-methylisophthalamide 293N¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 2952-(3-{2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-iodobenzyl)amino]-2-oxoethyl}phenoxy)acetamide 297N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 299N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-ethylhexyl)-5-methyl-N′,N′-dipropylisophthalamide 301N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(6-methoxypyidin-3-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide 303N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(2,4-dimethoxypyrimidin-5-yl)benzyl]-5-methyl-N′,N′-dipropylisophtalamide 305N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-ethylbutanoyl)benzamide 307N-[(2R,38)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide 309 N¹-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 311(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-[2′-(aminocarbonyl)biphenyl-4-yl]-4-oxobutanoate 3131-(3-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-5-methylbenzoyl)-L-prolinamide 315N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide 317N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-hydroxy-1-phenylpropyl)-5-methyl-N′,N′-dipropylisophthalamide 319N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′[2-(dimethylamino)ethyl]-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamide321N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxamide 3232-(5-acetyl-2-thienyl)-N-[(2R,3S)-3-amino-4-(3,5 -difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)acetamide 325N¹-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 327N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-diisopropyl-5-methylisophthalamide 329N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(methylsulfonyl)amino]benzamide 331N¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 333N-[(2R,3S)-3-amino-4-(3,5-difluoropheny1)-2-hydroxybutyl]-N-(3-iodobenzyl)-2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetamide 335 N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 337N¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 339

341

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(1-methyl-1H- imidazol-4-yl)sulfonyl]amino}benzamidetrihydrochloride 343

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-methyl-N-pentyl-N′,N′- dipropylisophthalamide 345 N¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 347N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 349N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-cyclohexyl-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamide 3512-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)ethyl (2,4-difluorophenyl)carbamate 353N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzamidehydrochloride 355N¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 357N¹-[(2R,3S)-3 -amino-4-(3-bromophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)- N³,N³-dipropylbenzene-1,3,5-tricarboxamide 359N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,8-dimethylquinoline-3-carboxamide 361N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(6-hydroxyhexyl)-5-methyl-N′,N′-dipropylisophthalamide 363N-[(2R,3S)-3-amino-4-(3,5 difluorophenyl)-2-hydroxybutyl]-N-[(2R)-2-hydroxypropyl]-5-methyl-N′,N′-dipropylisophthalamide 365N-[(2R,3S-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]propanamide 367N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)3-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzamide 369N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(4-phenylbutyl)-N′,N′-dipropylisophthalamide 371N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-7-(1H-imidazol-1-yl)-N-(3-iodobenzyl)-5,6-dihydronaphthalene-2-carboxamide 3733-(acetylamino)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-375 N-[(2R,3S)-3-amino-4-(3 ,5 -difluorophenyl)-2-hydroxybutyl]-N-[2-(3-ethylbenzyl)-4-methylbenzamide 377N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[2-(ethylthio)ethy]-5-methyl-N′,N′-dipropylisophthalamide 379N-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 381

383

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(2-hydroxypropyl)-5-methyl- N′,N′-dipropylisophthalamide 385N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-butoxypropyl)-5-methyl-N′N′-dipropylisophthalamide 387N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[2-(2-hydroxyethyl)piperidin-1-yl]carbonyl}-5-methylbenzamide 389methyl N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}-β-alaninate 391N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1-hydroxy-2-propylpentyl)benzamide 393N¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 395N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-[(methylsulfonyl)amino]butanamide trifluoroacetate (salt) 397N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(1-benzothien-2-yl)benzyl]-5-methyl-N′,N′-propylisophthalamide 399N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(benzyloxy)-N-(3-ethylbenzyl)isoxazole-5-carboxamide 401

403 1-(3-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-5-methylbenzoyl)-D-prolinamide 405N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1H-pyrazol-1-yl)pentanamide 407N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1-(2-furylmethyl)-5-oxopyrrolidine-3-carboxamide 409N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-ethyl-N-(3-methoxybenzyl)hexanamide hydrochloride 411N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(5-hydroxypentyl)-5-methyl-N′,N′-dipropylisophthalamide 413N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylpiperidine-1,3-dicarboxamide 415N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl[-N³,N^(3-diethyl-N)¹- (3-methoxybenzyl)piperidine-1,3-dicarboxamide 417N-[(2R,35)-3-amino-2-hydroxy-4-(pentafluorophenyl)butyl]-5-bromo-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamide 419N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-[(methylsulfonyl)aminolbenzamide 421

423

N-[(2R,3S)-3-amino-4-(3- bromophenyl)-2-hydroxybutyl]-3-[(dipropylamino) sulfonyl]-N-(3-methoxy benzyl)propanamide 425N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 427N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethoxypropyl)-5-methyl-N′,N′-dipropylisophthalamide 429N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 431

433N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-(phenylsulfonyl)butanamide hydrochloride 435N¹-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N3-dipropylbenzene-1,3,5-tricarboxamide 437N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 438(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3,3-dimethylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 440(1R,25)-2-amino-1-[(benzylamino)methyl]-3-(3-bromophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 442(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 444

446 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1,3-diphenylpropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 448 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-1-(hydroxymethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]benzoate 450(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(3S)-2-oxoazepan-3-yl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 452(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(cyclohexylamino)-5-oxopentanoate 454(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methylphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 456(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3- ethylbenzyl)amino]methyl)propyl N-[(2-propylpentyl)sulfonyl]-β-alaninate trifluoroacetate 458

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1,3-thiazol-2-yl)benzoate dihydrochloride460

(1R,2S)-2-amino-3-(2-furyl)-1- {[(3-methoxybenzyl)amino]methyl}propyl3-[(dipropyl amino)carbonyl]-5- methylbenzoate 462(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[methyl(phenyl)amino]propyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 464(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methylphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 466(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 5-oxo-1-(2-thienylmethyl)pyrrolidine-3-carboxylate 468 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(butylthio)methyl]-5-methyl-2-furoate470 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-{[(2-hydroxyethyl)amino]sulfonyl}benzoat 472(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[3-(trifluoromethyl)benzoyl]glycinate474 (1R,25)-2-amino-3-(3,5-difluorophenyl)-1-methylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 476 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-oxo-1,3-oxazolidin-3-yl)benzoate478 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-pyrrol-1-yl)benzoate 480(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 482(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl1,3,4,5-tetrahydrothiopyrano[4,3-b]indole-8- carboxlate 484(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[2-(trifluoromethyl)phenyl]amino}butanoate 486(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 488(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4,5-dimethyl-2-(1H-pyrrol-1-yl)thiophene-3- carboxylate 490(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2,3-dihydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 492 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2S)-2-hydroxypropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 494 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-1-methylpropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 496 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-chloro-4-(methylsulfonyl)benzoate 498(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxyethyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 500(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methoxyphenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate 502(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{methyl[(trifluoromethyl)sulfonyl]amino}benzoate hydrochloride 504(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 3-hydroxy-6-(1-hydroxy-2,2-dimethylpropyl)pyridine-2-carboxylate 506(1R,2S)-2-amino-1-{[(1,3-dicyclohexylpropyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 508(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 2,2′-bithiophene-5-carboxylate 510(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-imidazol-1-yl)butanoate 512(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl2,3-dihydroxy-4-[(4-methoxyphenyl)amino]- 4-oxobutanoate 514(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-hydroxyphenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 516(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 518(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2-thienyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 520(1R,2S)-2-amino-1-({[2-(aminocarbonyl)-1H-indol-6-yl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 522(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-bromophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 524(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl N-[4-(trifluoromethyl)benzoyl]glycinate526 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoate 528 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3,4-dichlorobenzoyl)glycinate 530(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-chloro-4-(methylsulfonyl)thiophene-2-carboxylate 532 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-ethylpropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 534(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({[(SR)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 536(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl5-methyl-7-(trifluoromethyl)pyrazolo[1,5- a]pyrimidine-2-carboxylate 538(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl N-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride540 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2,3-dimethylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 542 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4,5-dimethoxy-1-benzothiophene-2-carboxylate 544(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 546(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 548(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 550(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-(3,5-dioxo-1,2,4-triazolidin-4-yl)benzoate 552(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-hydroxy-3-[(3 -methoxyphenyl)sulfonyl]propanoate hydrochloride 554

556

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(2-methylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 558

(1R,2S)-2-amino-1-{[(2-{4-[(3-chlorobenzyl)oxy]phenyl}ethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3- [(dipropylamino)carbonyl]-5- methylbenzoate 560(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-(3-thienyl)butanoate562 (1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 564(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-[3-(trifluoromethyl)phenyl]butanoate 566(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 568(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)-3-(methylthio)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 570 (1R,2S)-2-amino-3-(3,5-difluorophenyl-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1H-1,2,3,-benzotriazol-1-yl)hexanoate572 (1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl-5-[(dipropylamino)carbonyl]benzoate 574(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 576(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-{[(trifluoromethyl)sulfonyl]amino}butanoate trifluoroacetate 578(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol 2-yl)acetate 580(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 582 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 584 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3,5-dichlorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 586(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl3-{[(2- hydroxyethyl)(propyl)amino]sulfonyl}propanoate hydrochloride 588(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(benzylthio)nicotinate 590(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-pyrazole-5-carboxylate 592(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-chloro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5 -carboxylate 594(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-benzimidazole-2-carboxylate 596(1R,2S)-2-amino-3-cyclohexyl-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 598(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-hydroxy-4,7-dimethoxy-1-benzofuran-5-carboxylate 600 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 602 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate 604(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-(2-thienyl)butanoate606 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3,5-dichlorophenyl)propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate 608(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-hydroxy-5-methylphenyl)-4-oxobutanoate 610 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-phenoxbenzoate 612(1R,2S)-2-amino-3-(3,5-difluorophenylyl- ethylbenzyl)amino]methyl}propyl4-[(aminocarbonyl)amino]benzoate 614(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-1-(hydroxymethyl)-3-(methylthio)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 616 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 7-hydroxy-4-oxochromane-2-carboxylate618(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-1-(hydroxymethyl)-3-methylbutyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 620 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-1-(hydroxymethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]benzoate 622(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-methyl-3-phenylpropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 439N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3,3-dimethylbutyl)-5-methyl-N′,N′-dipropylisophthalamide 441N¹-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 443N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 445

447

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(1,3-diphenylpropyl)-5- methyl-N′,N′- dipropylisophthalamide449

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-[(1S)-1-(hydroxy methyl)propyl]-N′,N′- dipropylisophthalamide451N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[(3S)-2-oxoazepan-3-yl]-N′,N′-dipropylisophthalamide 453N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-cyclohexyl-N-(3-ethylbenzyl)pentanediamide 455N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 457N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N^(3-[(2-propylpentyl)sulfonyl]-β-alaninamide trifluoroacetate (salt))459N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1,3-thiazol-2-yl)benzamide dihydrochloride 461N-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 463N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3-[methyl(phenyl)amino]propyl}-N′,N′-dipropylisophthalamide 465N¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 467N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-oxo-1-(2-thienylmethyl)pyrrolidine-3-carboxamide 469N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-[(butylthio)methyl]-N-(3-ethylbenzyl)-5-methyl-2-furamide 471N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2-hydroxyethyl)amino]sulfonyl}benzamide 473

475

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methyl cyclohexyl)-N′,N′- dipropylisophthalamide477N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-oxo-1,3-oxazolidin-3-yl)benzamide 479N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-pyrrol-1-yl)benzamide 481N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-5-methyl-N′,N′-dipropylisophthalamide483N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1,3,4,5-tetrahydrothiopyrano[4,3-b]indole-8-carboxamide 485N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-[2-(trifluoromethyl)phenyl]succinamide 487N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 489N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,5-dimethyl-2-(1H-pyrrol-1-yl)thiophene-3-carboxamide 491N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2,3-dihydroxypropyl)-5-methyl-N′,N′-dipropylisophthalamide 493N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2S)-2-hydroxypropyl]-5-methyl-N′,N′-dipropylisophthalamide 495N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[(1R)-1-methylpropyl]-N′,N′-dipropylisophthalamide 497N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-chloro-N-(3-ethylbenzyl)-4-(methylsulfonyl)benzamide 499N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-hydroxyethyl)-5-methyl-N′,N′-dipropylisophthalamide 501N-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 503N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{methyl[(trifluoromethyl)sulfonyl]amino}benzamide hydrochloride 505N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-hydroxy-6-(1-hydroxy-2,2-dimethylpropyl)pyridine-2-carboxamide 507N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(1,3-dicyclohexylpropyl)-5-methyl-N′,N′-dipropylisophthalamide 509N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,2′-bithiophene-5-carboxamide 511N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-imidazol-1-yl)butanamide 513N-[(2R,3S)-3-amino-4-(3,5-difluoropheny1)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dihydroxy-N′-(4-methoxyphenyl)succinamide 515N-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 517N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 519N¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 521N-[2-(aminocarbonyl)-1H-indol-6-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-diproylisophthalamide 523N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 525

527

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)- 2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanamide 529

531N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-chloro-N-(3-ethylbenzyl)-4-(methylsulfonyl)thiophene-2-carboxamide 533N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(1-ethylpropyl)-5-methyl-N′,N′-dipropylisophthalamide 535N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{[(5R)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-5-methyl-N′,N′-dipropylisophthalamide537N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide 539N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamidehydrochloride 541N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2,3-dimethylcyclohexyl)-5-methyl-N′,N′-dipropylisophthalamide 543N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,5-dimethoxy-1-benzothiophene-2-carboxamide 545N-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-N¹-(3-methylbutyl)-N³,N³-diproylbenzene-1,3,5-tricarboxamide 547N-[(2R,3S)-3-amino-4-(3 ,5-difluorophenyl)-2-hydroxybutyl]-N-{[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-5-methyl-N′,N′-dipropylisophthalamide549 N¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-(3-methoxylbenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 551N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,5-dioxo-1,2,4-triazolidin-4-yl)-N-(3-ethylbenzyl)benzamide 553N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(3-methoxyphenyl)sulfonyl]propanamide hydrochloride555

557N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(2-methylcyclohexyl)-N′,N′-dipropylisophthalamide 559N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-{4-[(3-chlorobenzyl)oxy]phenyl}ethyl)-5-methyl-N′,N′-dipropylisophthalamide 561N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-(3-thienyl)butanamide 563N¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 565N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide 567N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 569N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(hydroxymethyl)-3-(methylthio)propyl]-5-methyl-N′,N′-dipropylisophthalamide571N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1H-1,2,3-benzotriazol-1-yl)-N-(3-ethylbenzyl)hexanamide 573N¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 575N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanamide 577N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)4-{[(trifluoromethyl)sulfonyl]amino}butanamide trifluoroacetate (salt)579N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide 581N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-hydroxypropyl)-5-methyl-N′,N′-dipropylisophthalamide 583N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(hydroxymethyl)propyl]-5-methyl-N′,N′-dipropylisophthalamide 585N¹-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 587N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}-N-(3-methoxybenzyl)propanamidehydrochloride 589N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(benzylthio)-N-(3-ethylbenzyl)nicotinamide 591N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-pyrazole-5-carboxamide 593N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethylbenzyl)-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxamide595N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-benzimidazole-2-carboxamide 597N¹-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 599N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-6-hydroxy-4,7-dimethoxy-1-benzofuran-5-carboxamide 601N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(4-methylcyclohexyl)-N′,N′-dipropylisophthalamide 603N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide 605N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-(2-thienyl)butanamide 607N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 609N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-hydroxy-5-methylphenyl)-4-oxobutanamide 611N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-phenoxybenzamide 6134-[(aminocarbonyl)amino]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)benzamide 615N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-1-(hydroxymethyl)-3-(methylthio)propyl]-5-methyl-N′,N′-dipropylisophthalamide617N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-7-hydroxy-4-oxochromane-2-carboxamide 619N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S-1-(hydroxymethyl)-3-methylbutyl]-5-methyl-N′,N′-dipropylisophthalamide 621N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)propyl]-N′,N′-dipropylisophthalamide 623N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(1-methyl-3-phenylpropyl)-N′,N′-dipropylisophthalamide 624(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxylate 626(1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 628 (1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfony]propanoate630 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-oxo-3-(pentylamino)propanoate 632(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzy)amino]methyl}propyl 3-(trifluoromethoxy)benzoate 634(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-dipropylamino)sulfonyl]propanoate636 (1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)sufonyl]propanoate 638(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 640(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-{[4-(acetylamino)phenyl]amino}-4-oxobutanoate 642 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1-cyanoethyl)benzoate 644(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 4-oxo-4-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]butanoate 646 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 648(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-(2-oxo-2-pyrrolidin-1-ylethoxy)phenyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 650(1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 652(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (1,1-dioxidotetrahydro-2-thienyl)acetate654 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-chlorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 656(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-hex-1-yn-1-ylnicotinate 658(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-[(dipropylamino)sulfonyl]propanoate 660(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methoxylsoxazole-5-carboxylate 662(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,3-dimethyl-1H-indole-7-carboxylate 664(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-chlorophenyl)-2-hydroxy-4-oxobutanoate 666 (1R,2S)-2-amino-3-(3-fluoro-4-methoxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 668(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl (1-methyl-1H-indol-3-yl)(oxo)acetate 670(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 672(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methylphenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate 674(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-fluoro-4-methylphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 676(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[5-(4-methylphenyl)-2H-tetrazol-2-yl]acetate 678(1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate680 (1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(2-thienyl)propyl3- (aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 682(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methyl-3-phenylisoxazole-4-carboxylate684 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-fluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 686(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(methylsulfonyl)acetyl]-N-pentylglycinate 688(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4-methoxybenzoyl)glycinate 690(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6-difluorobenzoyl)glycinate 692(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-indol-3-yl)-4-oxobutanoate 694(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-[(5-benzyl-1,3,4-thiadiazol-2-yl)amino]-4- oxobutanoate 696(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-fluoro-4-methoxyphenyl)-4-oxobutanoate 698 ethyl 4-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}oxy)butyl]amino}piperidine-1-carboxylate 700 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-(2-fluorobenzoyl)-1H-pyrrole-2-carboxylate 702(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-chlorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 704(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 706(1R,2S)-2-amino-3-(4-hydroxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 708(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (4-morpholin-4-ylphenyl)acetate 710(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-[(dipropylamino)sulfonyl]propanoate712 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[benzyl(1-cyclopropylethyl)amino]-4-oxobutanoate 714 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(2,5-dimethylbenzoyl)-5-methylbenzoate 716 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(2-methoxy-5-methylphenyl)amino]-4-oxobutanoate 718 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3-hydroxyphenyl)acetate 720(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[hydroxy(2-methylphenyl)methyl]-5-methylbenzoate 722 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(ethylthio)nicotinate 724(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-[4-(2-furoyl)piperazin-1-yl]-4-oxobutanoate 726(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-fluoro-4-methylphenyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 728(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-oxoisoindoline-1-carboxylate 730(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(ethylthio)benzoate 732(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl thieno[2,3-b]guinoline-2-carboxylate 734(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4-methyl-1,3-oxazol-2-yl)benzoatehydrochloride 736(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-fluorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 738(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[2-furoyl(methyl)amino]benzoate 740(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-(3-methoxyphenyl)-4-oxobutanoate 742(1R,2S)-2-amino-1-[(cycloheptylamino)methyl]-3-(3,5-difluorophenyl)propyl3- [(dipropylamino)carbony]-5-methylbenzoate 744(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(4-methylphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 746(1R,2S)-2-amino-3-(3-fluoro-5-hydroxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoatehydrochloride 748 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-hydroxy-1H-indole-2-carboxylate 750(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-ethylbenzyl)amino]methyl}propyl 2,2-dimethylchromane-8-carboxylate 752(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-benzylpyrazine-2-carboxylate 4-oxide754 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl{2-[(dipropylamino)sulfonyl]ethyl}carbamate 756(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)-2-methylpropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 758(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-chlorosfluorophenyl)propyl3- [(dipropylamino)sulfonyl]propanoate 760(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-methoxyphenyl)-4-oxobutanoate 762(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-hydroxyphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 764(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-4-oxo-3,4-dihydrophthalazine-1-carboxylate 766 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3,4-dihydro-2H-1,5-benzodioxepine-7-carboxylate 768 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[4-(2,5-dioxopyrrolidin-1-yl)phenoxy]acetate 770(1R,2S)-2-amino-3-(2-furyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 772(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate 774(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 776

778

(1R,2S)-2-amino-3-(3-chloro- 5-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5- (dipropylamino)-5- oxopentanoate780

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-fluoro-2-hydroxyquinoline-4-carboxylate 782

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-(2-thienyl) butanoate 784

786(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(phenylthio)propyl3- (aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 788(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-1-(hydroxymethyl)-2-methylpropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 790(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R,2S)-1-(hydroxymethyl)-2-methylbutyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 792 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(phenoxymethyl)benzoate 794(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(2,4-difluorophenyl)amino]-5-oxopentanoate 796 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(4,6-dimethylpyrimidin-2-yl)amino]-5-oxopentanoate 798 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(3-methoxybenzoyl)-5-methylbenzoate800 (1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 802(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-dichlorophenyl)-4-oxobutanoate804 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[4-(methoxycarbonyl)phenyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 806 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl5-[(4-acetylphenyl)amino]-5-oxopentanoate 808(1R,2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 810(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(phenylthio)propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate 812(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-({2-[(methylamino)carbonyl]phenyl}thio)propanoate 814(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-[(1-propylbutyl)thio]propanoate hydrochloride 816(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(4-ethoxyphenyl)amino]-4-oxobutanoate818 (1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 820(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-({[(3-methoxyphenyl)amino]carbonyl}oxy)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 625N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2,3-dihydro-1-benzofuran-5-yl)-N-(3-ethylbenzyl)-1,3-thiazole-4-carboxamide 627N-{(2R,3-S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 629N-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 631N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-pentylmalonamide 633N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(trifluoromethoxy)benzamide 635N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 637N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyly)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 639N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanamide 641N′-[4-(acetylamino)phenyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl-N-(3-ethylbenzyl succinamide 643N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(1-cyanoethyl)-N-(3-ethylbenzyl)benzamide 645N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(5-phenyl-1,3,4-thiadiazol-2-yl)succinamide 647N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-benzyl-N³,N³-diproplbenzene-1,3,5-tricarboxamide 649N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[2-(2-oxo-2-pyrrolidin-1-ylethoxy)phenyl]-N′,N′-dipropylisophthalamide 651N¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 653N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1,1-dioxidotetrahydro-2-thienyl)-N-(3-ethylbenzyl)acetamide 655N-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 657N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hex-1-yn-1-ylnicotinamide 659N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 661N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methoxyisoxazole-5-carboxamide 663N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dimethyl-1H-indole-7-carboxamide 665N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3-chlorophenyl)-N-(3-ethylbenzyl)-2-hydroxy-4-oxobutanamide 667N¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methoxyphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 669N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(1-methyl-1H-indol-3-yl)-2-oxoacetamide 671N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 673N-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl)-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 675N¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 677N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[5-(4-methylphenyl)-2H-tetrazol-2-yl]acetamide 679N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 681N¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 683N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-3-phenylisoxazole-4-carboxamide 685N-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 687N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-[(methylsulfonyl)acetyl]-N²-pentylglycinamide 689

691

693

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-indol- 3-yl)-4-oxobutanamide 695N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(5-benzyl-1,3,4-thiadiazol-2-yl)-N-(3-ethylbenzyl)succinamide 697N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(3-fluoro-4-methoxyphenyl)-4-oxobutanamide 699 ethyl4-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)piperidine-1-carboxylate701N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-fluorobenzoyl)-1H-pyrrole-2-carboxamide 703N¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 705N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 707N-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 709N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(4-morpholin-4-ylphenyl)acetamide 711N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 713N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-benzyl-N′-(1-cyclopropylethyl)-N-(3-ethylbenzyl)succinamide 715N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2,5-dimethylbenzoyl)-N-(3-methoxybenzyl)-5-methylbenzamide 717N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(2-methoxy-5-methylphenyl)succinamide 719N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(3-hydroxyphenyl)acetamide 721N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-[hydroxy(2-methylphenyl)methyl]-N-(3-methoxybenzyl)-5-methylbenzamide 723N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(ethylthio)nicotinamide 725N-[(2R,3S--3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-[4-(2-furoyl)piperazin-1-yl]-4-oxobutanamide 727N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 729N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-oxoisoindoline-1-carboxamide 731N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(ethylthio)benzamide 733N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)thieno[2,3-b]quinoline-2-carboxamide 735N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(4-methyl-1,3-oxazol-2-yl)benzamide hydrochloride 737N¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 739N-(2-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}phenyl)-N-methyl-2-furamide 741N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-(3-methoxyphenyl)-4-oxobutanamide 743N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-cycloheptyl-5-methyl-N′,N′-dipropylisophthalamide 745N¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 747N-[(2R,3S)-3-amino-4-(3-fluoro-5-hydroxyphenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide hydrochloride749N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hydroxy-1H-indole-2-carboxamide 751N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,2-dimethylchromane-8-carboxamide 753N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-benzyl-N-(3-ethylbenzyl)pyrazine-2-carboxamide 4-oxide 7552-({[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-methoxybenzyl)amino]carbonyl}amino)-N,N-dipropylethanesulfonamide 757N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-5-methyl-N′,N′-dipropylisophthalamide759N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-benzyl-3-[(dipropylamino)sulfonyl]propanamide 761N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(4-methoxyphenyl)-4-oxobutanamide 763N¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 765N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methyl-4-oxo-3,4-dihydrophthalazine-1-carboxamide 767N-[(2R,3S-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3,4-dihydro-2H-1,5-benzodioxepine-7-carboxamide 769N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[4-(2,5-dioxopyrrolidin-1-yl)phenoxy]-N-(3-ethylbenzyl)acetamide 771N¹-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 773N-[(2R,3S)-3-aminoo-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3]pyrimidine-6-carboxamide 775N¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 777

779 N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamide 781N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyly)-6-fluoro-2-hydroxyguinoline-4-carboxamide 783N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-oxo-4-(2-thienyl)butanamide 785N³-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-methoxybenzyl)amino]carbonyl}-N¹,N¹-dipropyl-β-alaninamide 787N¹-[(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butylyN¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 789N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-5-methyl-N′,N′-dipropylisophthaIamide791N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R,2S)-1-(hydroxymethyl)-2-methylbutyl]-5-methyl-N′,N′-dipropylisophthalamide 793N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(phenoxymethyl)benzamide 795N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(2,4-difluorophenyl)-N-(3-ethylbenzyl)pentanediamide 797N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(4,6-dimethylpyrimidin-2-yl)-N-(3-ethylbenzyl)pentanediamide 799N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(3-methoxybenzoyl)-N-(3-methoxybenzyl)-5-methylbenzamide 801N-{(2R,3S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 803N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dichlorophenyl)-N-(3-ethylbenzyl)-4-oxobutanamide 805 methyl4-{(2S,3R)-2-amino-4-[{3-[(dipropylamino)carbonyl]-5-methlbenzoyl}(3-methoxybenzyl)amino]-3-hydroxybutyl}benzoate 807N¹-(4-acetylphenyl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)pentanediamide 809N-{(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutyl}-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 811N-[(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 8132-({3-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-3-oxopropyl}thio)-N-methylbenzamide 815N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-3-[(1-propylbutyl)thio]propanamide hydrochloride 817N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(4-ethoxyphenyl)-N-(3-ethylbenzyl)succinamide 819N¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 8212-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)ethyl (3-methoxyphenyl)carbamate 822(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(benzyloxy)benzoate 824(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-2-hydroxy-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 826 (1R,2S)-2-amino-3-(pentafluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate 828(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-hydroxyphenyl)-4-oxobutanoate 830(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-[(dipropylamino)sulfonyl]propanoate 832(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(piperidin-3-ylsulfonyl)benzoatedihydrochloride 834 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl6-chloro-4-hydroxyguinoline-2-carboxylate 836(1R,2AS)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(2-thienyl)propyl5- (dipropylamino)-5-oxopentanoate 838(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-4-methylpentyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 840(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(6-oxo-3-phenylpyridazin-1(6H)-yl)acetate 842(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{4-[(methylsulfonyl)amino]phenyl}propanoate 844(1R,2S)-2-amino-3-(4-fluoro-3-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 846(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-methylphenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 848(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 3-(2-chlorophenoxy)propanoate 850(1R,2S)-2-amino-3-(4-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 852(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4-chlorobenzoyl)-D-alaninate 854(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoatehydrochloride 856 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-methylphenyl)-4-oxobutanoate 858(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[3-(trifluoromethyl)phenyl]amino}butanoate 860(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 862 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (5-pyridin-2-yl-2H-tetrazol-2-yl)acetate864

866

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-(3-methylphenyl)propyl 3-[(dipropyl amino)sulfonyl]propanoate 868(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl isoxazole-5-carboxylate 870(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3,5-dimethoxyphenoxy)acetate 872(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-hydroxybenzoate 874 (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5-oxopentanoate 876(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-{[5-(cyclopentylmethyl)-1,3,4-thiadiazol-2- yl]amino}-4-oxobutanoate878(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethyl)phenyl]propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 880(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(3-oxo-1,2-benzisothiazol-2(3H)-yl)acetate 882(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-methyl-5-(pyrrolidin-1-ylcarbonyl)-1H-pyrrol-3-yl]amino}methyl)propyl3-[(dipropylamino)carbonyl]- 5-methylbenzoate 884(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-4-oxobutanoate886 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-naphthyl)-4-oxobutanoate 888(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4,6-diethoxypyridine-2-carboxylate 890(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-(5-methyl-1H-pyrrol-2-yl)-4-oxobutanoate 892(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-({[2-(methylamino)ethyl]amino}sulfonyl)benzoate hydrochloride 894(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-methyl-5-(4-methylbenzoyl)benzoate896(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-[(benzylamino)methyl]propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate 898(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(piperazin-1-ylsulfonyl)benzoatehydrochloride 900(1R,2S)-2-amino-1-[({2-[4-(aminosulfonyl)phenyl]ethyl}amino)methyl]-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 902(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-hydroxy-1-(hydroxymethyl)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 904 (1R,2S)-2-amino-3-(4-fluoro-3-methylphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 906(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(3-oxo-2,1-benzisothiazol-1(3H)-yl)propanoate 908 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2,6-dihydroxypyrimidin-4-yl)acetate 910(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 5-(dipropylamino)-5-oxopentanoate 912(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-hydroxyphenyl)propyl 3-[(dipropylamino sulfonyl]propanoate 914(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-2-methyl-4-oxobutanoate 916 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-5-[(2-pyridin-2-ylethyl)amino]pentanoate 918(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetate 920 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(anilinocarbonyl)glycinate 922(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6-dimethoxybenzoyl)glycinate 924(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1,3-dithian-2-yl)-3-furoate 926(1R,2S)-2-amino-3-(3,5-difluorophenyl) 1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[2-oxo-2-(propylamino)ethyl]benzoate928 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-bromophenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate 930(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 3-(2-fluorophenyl)propanoate 932(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methylthiophene-2-carboxylate 934(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [4-(benzyloxy)phenyl]acetate 936(1R,2S)-2-arnino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[(5,7-dimethyl[1,2,4]triazolo[4,3-a]pyrimidin- 3-yl)thio]acetate 938(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(1-acetyl-2,3-dihydro-1H-indol-7-yl)amino]-4-oxobutanoate 940(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl5-[(3-acetylphenyl)amino]-5-oxopentanoate 942(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4-chlorophenoxy)-2-hydroxypropanoate944N³-[(1S,2R)-3-(benzylamino)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxypropyl]-N¹,N¹-dipropylbenzene-1,3,5-tricarboxamide 946(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 948(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-indole-7-carboxylate 950(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(3-methylphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 952(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1,2,3-thiadiazol-4-yl)benzoate 954(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methoxybenzyl)amino]methyl propyl 3-[(dipropylamino)sulfonyl]propanoate956 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 958(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(4-methylphenyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 960(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-fluoros-5-(trifluoromethyl)phenyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 962(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [1-methyl-3-(methylthio)-1H-indol-2-yl]acetate 964 (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 966 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[(2-{[4-(1,3-oxazol-5-yl)phenyl]amino}-2- oxoethyl)thio]acetate 968

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-furyl)-4- oxobutanoate 970

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)propanoate 972

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [2-(acetylamino)-1,3-thiazol-4-yl]acetate 974 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(4-methyl-4H-1,2,4-triazol-3-yl)thio](phenyl)acetate 976(1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 978(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1,3-benzothiazol-2-yl)butanoate 980(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(3-chloro-4-fluorophenyl)amino]-4-oxobutanoate 982(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 984 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(2-oxo-2,3-dihydroquinazolin-4-yl)thio]acetate 823N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(benzyloxy)-N-(3-ethylbenzyl)benzamide 825N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-2-hydroxy-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamide 827N-[(2R,3S)-3-amino-2-hydroxy-4-(pentafluorophenyl)butyl]-5-methyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamide 829N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(4-hydroxyphenyl)-4-oxobutanamide 831N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 833N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(piperidin-3-ylsulfonyl)benzamide dihydrochloride 835N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethylbenzyl)-4-hydroxyquinoline-2-carboxamide 837N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamide 839N-[(2R,3S)-3-amino-2-hydroxy-5-methylhexyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide 841N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(6-oxo-3-phenylpyridazin-1(6H)-yl)acetamide 843N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)3-{4-[(methylsulfonyl)amino]phenyl}propanamide 845N¹-[(2R,3.S)-3-amino-4-(4-fluoro-3-methylphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 847N-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 849N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-chlorophenoxy)-N-(3-iodobenzyl)propanamide 851N¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 853

855

N-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3- methoxybenzyl)propanamide hydrochloride 857

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)- 4-(4-methylphenyl)-4- oxobutanamide 859

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[3-(trifluoromethyl)phenyl]amino}butanoate 861

N-[(2R,3S)-3-amino-4-(1,3- benzodioxol-5-yl)-2-hydroxybutyl]-N-(3-methoxybenzyl)- 5-methyl-N′,N′- dipropylisophthalamide 863

865

867 N-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 869N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl isoxazole-5-carboxamide 871N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(3,5-dimethoxyphenoxy)-N-(3-ethylbenzyl)acetamide 873N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(3-ethylbenzyl)-3-hydroxybenzamide 875N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamide 877N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-[5-(cyclopentylmethyl)-1,3,4-thiadiazol-2-yl]-N-(3-ethylbenzyl)succinamide879N¹-{-2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 881N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(3-oxo-1,2-benzisothiazol-2(3H)-yl)acetamide 883N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[1-methyl-5-(pyrrolidin-1-ylcarbonyl)-1H-pyrrol-3-yl]-N′,N′-dipropylisophthalamide 885N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethylbenzyl)-4-oxobutanamide 887N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-naphthyl)-4-oxobutanamide 889N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4,6-diethoxy-N-(3-ethylbenzyl)pyridine-2-carboxamide 891N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(5-methyl-1H-pyrrol-2-yl)-4-oxobutanamide 893N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-({[2-(methylamino)ethyl]amino}sulfonyl)benzamide hydrochloride 895N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-3-methyl-5-(4-methylbenzoyl)benzamide 897N-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 899N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(piperazin-1-ylsulfonyl)benzamide hydrochloride 901N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{2-[4-(aminosulfonyl)phenyl]ethyl}-5-methyl-N′,N′-dipropylisophthalamide 903N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]-5-methyl-N′,N′-dipropylisophthalamide 905N¹-[(2R,3S)-3-amino-4-(4-fluoro-3-methylphenyl)-2-hydroxybutylpN¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 907N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(3-oxo-2,1-benzisothiazol-1(3H)-yl)propanamide 909N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2,6-dihydroxyprimidin-4-yl)-N-(3-ethylbenzyl)acetamide 911N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N-(3-methoxybenxyl)-N′,N′-dipropylpentanediamide 913N-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N-benzyl-3-[(dipropylamino)sulfonyl]propanamide 915N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethylbenzyl)-2-methyl-4-oxobutanamide 917N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(2-pyridin-2-ylethyl)pentanediamide 919N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetamide 921N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(anilinocarbonyl)-N¹-(3-ethylbenzyl)glycinamide 923

925

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-2-(1,3-dithian-2-yl)- N-(3-ethylbenzyl)-3- furamide 927

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2- [2-oxo-2-(propylamino) ethyl]benzamide 929N-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-benzyl-3-[(dipropylamino)sulfonyl]propanamide 931N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-fluorophenyl)-N-(3-iodobenzyl)propanamide 933N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methylthiophene-2-carboxamide 935N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[4-(benzyloxy)phenyl]-N-(3-iodobenzyl)acetamide 937N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[(5,7-dimethyl[1,2,4]triazolo[4,3-a]pyrimidin-3-yl)thio]-N-(3-ethylbenzyl)acetamide939 N′-(1-acetyl-2,3-dihydro-1H-indol-7-yl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)succinamide 941N′-(3-acetylphenyl)-N-[(2R,3-S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)pentanediamide 943N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4-chlorophenoxy)-N-(3-ethylbenzyl)-2-hydroxypropanamide 945N³-[(1S,2R)-3-(benzylamino)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxypropyl]-N¹,N¹-dipropylbenzene-1,3,5-tricarboxamide 947N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 949N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-indole-7-carboxamide 951N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-diproplbenzene-1,3,5-tricarboxamide 953N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1,2,3-thiadiazol-4-yl)benzamide 955N-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 957N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanamide 959N-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 961N-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 963N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[1-methyl-3-(methylthio)-1H-indol-2-yl]acetamide 965N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 9672-({2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-2-oxoethyl}thio)-N-[4-(1,3-oxazol-5-yl)phenyl]acetamide969N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-furyl)-4-oxobutanamide 971N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)propanamide 9732-[2-(acetylamino)-1,3-thiazol-4-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)acetamide 975N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(4-methyl-4H-1,2,4-triazol-3-yl)thio]-2-phenylacetamide 977N-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 979N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(1,3-benzothiazol-2-yl)-N-(3-ethylbenzyl)butanamide 981N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3-chloro-4-fluorophenyl)-N-(3-ethylbenzyl)succinamide 983N-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 985N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(2-oxo-2,3-dihydroquinazolin-4-yl)thio]acetamide 986(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-methyl-5-(2-methylbenzoyl)benzoate988 (1R,2S)-2-amino-3-(4-hydroxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5-oxopentanoate 990(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 992(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3- ethylbenz)amino]methyl}propyl 4-propoxybenoate 994(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}1-methyl-1H-indole-2-carboxylate 996(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzoate 998 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-2-methoxy-4-oxobutanoate 1000 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [3-(2-thienyl)-1H-pyrazol-1-yl]acetate1002 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5 -anilino-5-oxopentanoate 1004(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(2-thioxo-1,3-benzothiazol-3(2H)-yl)acetate 1006(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-cyclohexylpropyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1008(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methoxyphenyl)propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1010(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenxyl)amino]methyl}propyl (3-hydroxy-4-methylphenyl)acetate 1012(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyly 1-{[(3-methylbutylL)amino]methyl}propy 3-[(dipropylamino)carbonyl]-5- 1014(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenzyl)amino]methyl}propyl7-fluoro-4H-imidazo[5,1-c][1,4]benzoxazine- 3-carboxyl ate 1016(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenzyl)amino]methyl}propyl4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)- 4-oxobutanoate 1018(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1-benzofuran-3-carboxylate 1020(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3,4-dichlorophenyl)amino]-3-oxopropanoate 1022(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-fluoro-5-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1024(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-hydroxy-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1026(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-methylphenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1028(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-5-(pyridin-3-ylamino)pentanoate1030 (1R,2S)-2-amino-3-(3,5-difluorophenyly-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-methyl-4-oxo-4H-chromene-6-carboxylate1032 (1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3-ethylbenzyl)amino]methyl}propyl ({2-[(5-methylisoxazol-3-yl)amino]-2-oxoethyl}thio)acetate 1034(1R,2S)-2-amino-3-(3,5-difluorophenyly-1-({[3-(1H-imidazol-1-yl)propyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 1036(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[dipropylamino)sulfonyl]propanoate1038(1R,2S)-2-amino-3-(4-hydroxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl3-[(dipropylamino)sulfonyl]propanoate 1040(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1042(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(2-thienyl)propyl 3-[(dipropylamino)sulfonyl]propanoate 1044(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(2,2-dimethylpropanoyl)amino]-2-hydroxybenzoate 1046 (1R,2S)-2-amino-3-(3-methoxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1048 (1R,2S)-2-amino-3-(4-fluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-{[(3-methoxybenzyl)amino]sulfonyl}benzoate 1050(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 1052(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-(2-furoylamino)hexanoate 1054(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(1-phenyl-4,5-dihydro-1H-tetrazol-5-yl)thio]acetate 1056(1S,2S)-2-amino-3-phenyl-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-{[(3-methoxybenzyl)amino]sulfonyl}benzoate 1058(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-dihydro-2H-chromen-6-yl)-4-oxobutanoate 1060 (1R,2S)-2-amino-3-(3-methoxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1062(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5-oxopentanoate 1064(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl indolizine-2-carboxylate 1066(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethoxy)phenyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate 1068(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl nicotinate 1-oxide 1070(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate1072 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [(aminocarbonyl)oxy]acetate 1074(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,3-dihydro-1H-cyclopenta[b]quinoline-9-carboxylate 1076 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-1H-pyrazole-5-carboxylate 1078(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(benzoylamino)pentanoate 1080(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(methoxymethyl)thio]benzoate 1082(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3- methoxypropanoate 1084(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(methylamino)carbonyl]amino}-3-(3-thienyl)propanoate 1086 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-pyridin-2-ylthiophene-2-carboxylate1088 (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(benzyloxy)-5-fluorophenyl]propyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1090(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (5,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyridin-3-yl)acetate 1092(1R,2S)-2-amino-3-(3-fluoro-4-methoxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1094 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl2-isobutyl-1,3-dioxoisoindoline-5-carboxylate 1096(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(acetylamino)-2-furoate 1098(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(4-methoxyphenyl)acetyl]glycinate1100 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl isoguinoline-4-carboxylate 1102(1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1104(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (4-hydroxy-3-methoxyphenyl)acetate 1106(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[(4-phenyl-4H-1,2,4-triazol-3-yl)thio]acetate 1108(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3,5-dimethoxyphenyl)acetate 1110(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-methoxyphenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1112(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2-ethyl-4H-[1,2,4]triazolo[1,5-a]benzimidazol-4-yl)acetate 1114(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2-furyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate 1116(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 7-chloro-1-benzofuran-2-carboxylate 1118(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate 1120 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-oxo-2H-1,3-benzoxazin-3(4H-yl)propanoate 1122 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}proply(pyrimidin-2-ylthio)acetate 1124(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-{[3-(aminocarbonyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]amino}-4-oxobutanoate 1126(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetate 1128(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl quinoline-6-carboxylate 1130(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2-furyl)propyl3-(aminocarbonyl)- 5-[(dipropylamino)carbonyl]benzoate 1132(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-oxobutanoate 1134 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(1H-indol-3-yl)-1H-pyrazole-5-carboxylate 1136(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-{[(methylamino)carbonothioyl]amino}benzoate 1138(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-chloronicotinate 1140(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-hydroxyphenyl)-4-oxobutanoate 1142(1R,2-)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (phthalazin-1-ylthio)acetate 1144(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(1-oxidopyridin-2-yl)thio]acetate 1146(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(acetylamino)-5-fluoro-1H-indole-2-carboxylate 1148(1S,2S)-2-amino-3-phenyl-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-{[(3-chlorobenzyl)amino]sulfonyl}benzoate 1150(1R,2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1152(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-[(benzylamino)methyl]propyl3-{[(3- (aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate 1154(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-{[(3-ethylbenzyl)amino]methyl}propyl4-(3,4-dichlorophenyl)-2-hydroxy-3-methyl- 4-oxobutanoate 1156(1R,2S)-2-amino-1-{[(3-methylbutyl)amino)methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-[(dipropylamino)sulfonyl]propanoate1158 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methyl}propyl4-[(5-methyl-1,3,4-thiadiazol-2-yl)amino]-4- oxobutanoate 1160(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2-ethyl-1H-benzimidazol-1-yl)acetate1162 (1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate1164 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-oxo-1,3-benzoxazol-3(2H)-yl)propanoat 1166 (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate1168 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(6-methylpyridin-2-yl)amino]-4-oxobutanoate 1170 4-((1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl) 3-ethyl (4R)-1,3-oxazolidine-3,4-dicarboxylate 987N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-3-methyl-5-(2-methylbenzoyl)benzamide 989

N-[(2R,3S)-3-amino-2- hydroxy-4-(4-hydroxyphenyl) butyl]-N-(3-methoxybenzyl)-N′,N′- dipropylpentanediamide 991

N¹-[(2R,3S)-3-amino-2- hydroxy-4-(4-methylphenyl)butyl]-N¹-benzyl-N³,N³- dipropylbenzene-1,3,5- tricarboxamide 993

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-4-propoxy benzamide 995

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-1-methyl-1H- indole-2- carboxamide 997

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-5-chloro-N-(3-ethylbenzyl)-2-(3-methyl- 4H-1,2,4-triazol-4-yl) benzamide 999

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethyl benzyl)-2-methoxy-4- oxobutanamide 1001

N-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-N-(3-ethylbenzyl)-2-[3-(2-thienyl)- 1H-pyrazol-1-yl]acetamide 1003N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-phenylpentanediamide 1005N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(2-thioxo-1,3-benzothiazol-3(2H)-yl)acetamide 1007N-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 1009N¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butyl]-N¹-(3-methoxybenzyl -N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1011N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(3-hydroxy-4-methylphenyl)acetamide 1013N-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-5-methyl-N-(3-methylbutyl)-N+40,N′-dipropylisophthalamide 1015N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-7-fluoro-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide 1017N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyll-4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-N-(3-ethylbenzyl)-4-oxobutanamide 1019N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1-benzofuran-3-carboxamide 1021N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3,4-dichlorophenyl)-N-(3-ethylbenzyl)malonamide 1023N¹-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1025N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-2-hydroxy-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamide 1027N-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 1029N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-pyridin-3-ylpentanediamide 1031(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-methyl-4-oxo-4H-chromene-6-carboxylate1033 2-({2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-2-oxoethyl}thio)-N-(5-methylisoxazol-3-yl)acetamide1035N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(1H-imidazol-1-yl)propyl]-5-methyl-N′,N′-dipropylisophthalamide 1037N-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 1039N-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 1041N-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 1043N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 1045N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-[(2,2-dimethylpropanoyl)amino]-N-(3-ethylbenzyl)-2-hydroxybenzamide 1047N-[(2R,3AS)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 1049N-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-3-{[(3-methoxybenzyl)amino]sulfonyl}-N-[3-(trifluoromethyl)benzyl]benzamide1051N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 1053N-{6-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-6-oxohexyl}-2-furamide 1055N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(1-phenyl-4,5-dihydro-1H-tetrazol-5-yl)thio]acetamide 1057N-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(3-methoxybenzyl)amino]sulfonyl}-N-[3-trifluoromethyl)benzyl]benzamide 1059N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dihydro-2H-chromen-6-yl)-N-(3-ethylbenzyl)-4-oxobutanamide 1061N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1063N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamide 1065N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)indolizine-2-carboxamide 1067N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 1069N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)nicotinamide 1-oxide 1071N-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 10732-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-iodobenzyl)amino]-2-oxoethyl carbamate 1075N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dihydro-1H-cyclopenta[b]guinoline-9-carboxamide 1077N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methyl-1H-yrazole-5-carboxamide 1079N-{5-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-5-oxopentyl}benzamide 1081N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-[(methoxymethyl)thio]benzamide 1083N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(1,3-benzothiazol-2-yl)-N-(3-ethylbenzyl)-3-methoxypropanamide 1085N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[methylamino)carbonyl]amino}-3-(3-thienyl)propanamide 1087N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-pyridin-2-ylthiophene-2-carboxamide 1089N¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1091N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(5,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyridin-3-yl)-N-(3-ethylbenzyl)acetamide1093N-[(2R,3S)-3-amino-4-(3-fluoro-4-methoxyphenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamide 1095N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-isobutyl-1,3-dioxoisoindoline-5-carboxamide 10975-(acetylamino)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-furamide 1099N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-[(4-methoxyphenyl)acetyl]glycinamide 1101N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)isoquinoline-4-carboxamide 1103N¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1105N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(4-hydroxy-3-methoxyphenyl)acetamide 1107N-[(2R,3-S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyly-N-(3-ethylbenzyl)2-[(4-phenyl-4H-1,2,4-triazol-3-yl)thio]acetamide 1109N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(3,5-dimethoxyphenyl)-N-(3-ethylbenzyl)acetamide 1111N-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 1113N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(2-ethyl-4H-[1,2,4]triazolo[1,5-a]benzimidazol-4-yl)acetamide 1115N-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyly-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide 1117N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-7-chloro-N-(3-ethylbenzyl)-1-benzofuran-2-carboxamide 1119N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(3-ethylbenzyl)propanamide 1121N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-oxo-2H-1,3-benzoxazin-3(4H)-yl)propanamide 1123N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(pyrimidin-2-ylthio)acetamide 1125N¹-[3-(aminocarbonyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)succinamide1127N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide 1129N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)quinoline-6-carboxamide 1131

N-[(2R,3S)-3-amino-4-(2- furyl)-2-hydroxybutyl]- N¹-benzyl-N³,N³-dipropylbenzene-1,3,5- tricarboxamide 1133

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-4-(2,3-dihydro-1,4- benzodioxin-6-yl)-N- (3-ethylbenzyl)-4-oxobutanamide 1135

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3- (1H-indol-3-yl)-1H-pyrazole- 5-carboxamide1137

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2- hydroxy-4-{[(methylamino)carbonothioyl]amino}benzamide 1139

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethyl benzyl)nicotinamide 1141

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4 -(3-hydroxyphenyl)-4- oxobutanamide 1143

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2 -(phthalazin-1-ylthio) acetamide 1145

N-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2 -[(1-oxidopyridin-2- yl)thio]acetamide 1147

3-(acetylamino)-N-[(2R,3S)- 3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]- N-(3-ethylbenzyl)-5-fluoro-1H-indole-2-carboxamide 1149N-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(3-chlorobenzyl)amino]sulfonyl}-N-[3-(trifluoromethyl)benzyl]benzamide 1151N¹-{(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1153N¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 1155N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dichlorophenyl)-N-(3-ethylbenzyl)-2-hydroxy-3-methyl-4-oxobutanamide1157N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 1159N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(5 -methyl-1,3,4-thiadiazol-2-yl)succinamide 1161N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2-ethyl-1H-benzimidazol-1-yl)-N-(3-ethylbenzyl)acetamide 1163N-[(2R,3S)-3-ammo-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide 1165N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-oxo-1,3-benzoxazol-3(2H)-yl)propanamide 1167N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamide 1169N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(6-methylpyridin-2-yl)succinamide 1171 ethyl(4R)-4-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-1,3-oxazolidine-3-carboxylate 1172(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfinyl)-N-(methoxycarbonyl)-D-alaninate 1174 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl S-butyl-N-(methoxycarbonyl)-D-cysteinate1176 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(4,4,4-trifluorobutyl)sulfonyl]-D-alaninate 1178(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(4,4,4-trifluorobutyl)sulfinyl]-D-alaninate 1180(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-S-(4,4,4-trifluorobutyl)-D-cysteinate 1182(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1184 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(2,2,2-trifluoroethoxy)carbonyl]-D-alaninate 1186(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(2-cyanoethoxy)carbonyl]-D-alaninate 1188(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-{[(3R)-pyrrolidin-3-yloxy]carbonyl}-D-alaninate 1190(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-D-alaninate 1192(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[2-(acetylamino)ethoxy]carbonyl}-3-(butylsulfonyl)-D-alaninate 1194(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(pyridin-3-ylmethoxy)carbonyl]-D-alaninate 1196(1R-2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(pyridin-4-ylmethoxy)carbonyl]-D-alaninate 1198(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl3- (butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1200(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl3- (butylsulfonyl)-N-[(2-cyanoethoxy)carbonyl]-D-alaninate 1202(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propylN-[(benzyloxy)carbonyl]-3-(butylsulfonyl)- D-alaninate 1204(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1206(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propylN- [(2-cyanoethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate1208(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propylN-{[2-(acetylamino)ethoxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninate1210 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-(methoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1212(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1214(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-{[2-(diethylamino)-2-oxoethoxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1216(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(methoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1218(1R,2S)-2-an-iino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(isopropoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1220(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(cyclopropylmethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1222(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(allyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1224(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-cyanoethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1226(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-{[2-(acetylamino)ethoxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1228(1R,2S)-2-amino-3-(3,5-difluorophenyly-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-3-ylmethoxy)carbonyl]-D-alaninate 1230(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-4-ylmethoxy)carbonyl]-D-alaninate 1232(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-{[(benzyloxy)carbonyl]amino}-4-(methylsulfonyl)butanoate 1234(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-D- alaninate 1236(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-L- alaninate 1238(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-hydroxy-1-phenylethyl]amino) methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1240(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1242(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-2-methoxy-1-phenylethyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)su1fonyl]-D-alaninate 1244(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino) methyl)propylN-[(benzyloxy)carbonyl]-3-[(1- propylbutyl)sulfonyl]-D-alaninate 1246(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(prop-2-yn-1- yloxy)carbonyl]-D-alaninate 1248(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-methoxyethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1250(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)aminolmethyl}propyl N-({[(3R)-1-acetylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1252(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-D-alaninate 1254(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-L-alaninate 1256(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1258(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-L-alaninate 1260(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propylN-[(benzyloxy)carbonyl]-3-[(1- propylbutyl)sulfonyl]alaninate 1262(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1264(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)aminolmethyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1266(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propylN- [(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1268(1R,2S)-2-amino-1-{[(cyclopropylmethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1270(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylphenyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1272(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({2-[3-(trifluoromethyl)phenyl]ethyl}amino)methyl]propylN-[(benzyloxy)carbonyl]-3- [(1-propylbutyl)sulfonyl]alaninate 1274(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-3- ylmethoxy)carbonyl]alaninate1276 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}alaninate 1278(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-tetrahydrofuran-3-yloxy]carbonyl}alaninate 1280(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}alaninate1282 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1-acetylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1284(1R,2S)-2-amino-3-(3,5-difluorophenyly 1-{[(3- ethylbenzyl)amino]methyl)propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-pyrrolidin-3-yloxy]carbonyl}alaninate 1286(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1-benzylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1288(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1,1-dioxidotetrahydro-3-thienyl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1290(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-tetrahydro-3-thienyloxy]carbonyl}alaninate 1292(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(cyclopentyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1294(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(cyclohexyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1296(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl3-[(1-propylbutyl)sulfonyl]-N-[(tetrahydro-2H-pyran-4-yloxy)carbonyl]alaninate1298

1300

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[1-(methylsulfonyl)piperidin-4-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1302

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[(1-acetylpiperidin-4-yl)oxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]alaninate 1304

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(2R)-5-oxopyrrolidin-2-yl]methoxy}carbonyl)-3-[(1-propylbutyl) sulfonyl]alaninate1306

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(2S)-5-oxopyrrolidin-2-yl]methoxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate1308

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-methoxyethoxy)carbonyl]-3-[(1-propylbutyl) sulfonyl]alaninate 1310

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-(butylsulfonyl) alaninate 1312(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1314N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-hydroxy-4-(phenylsulfonyl)butanamide hydrochloride 1316(1R,2LS)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN²-[(benzyloxy)carbonyl]-N⁵,N⁵-dipropyl-L- glutaminate 1318(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)an-iino]methyl}propylN²-[(benzyloxy)carbonyl]-N⁵,N⁵-dipropyl-D- glutaminate 1320(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(3,3,3-trifluoropropanoyl)-D-alaninate 1322(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(trifluoroacetyl)-D-alaninate 1324 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-3-(butylsulfonyl)-D-alaninate1326 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-isonicotinoyl-D-alaninate 1328(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methy-}propyl3-(butylsulfonyl)-N-(cyclopropylcarbonyl)-D- alaninate 1330(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl β-alanyl-3-(butylsulfonyl)-D-alaninate1332 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl glycyl-3-(butylsulfonyl)-D-alaninate1334 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N,N-dimethylglycyl-3-(butylsulfonyl)-D-alaninate 1336 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN,N-dimethyl-β-alanyl-3-(butylsulfonyl)-D- alaninate 1338(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxyacetyl)-D-alaninate 1340 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-(pyridin-3-ylcarbonyl)-D- alaninate 1342(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-D-alaninate 1344(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-{[3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}-D-alaninate 1346(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5- yl)carbonyl]-D-alaninate1348 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(1H-imidazol-4-ylcarbonyl)-D-alaninate 1350(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-hydroxy-2-[(methoxycarbonyl)amino]nonanoate 1352(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-[(6-hydroxypyridin-3- yl)carbonyl]-D-alaninate 1354(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl3- (butylsulfonyl)-N-(pyridin-3-ylcarbonyl)-D-alaninate 1356(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-acetyl-3-(butylsulfonyl)-D-alaninate1358(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propylN- (cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1360(1R,28)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-acetyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1362 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)aminolmethyl}propylN-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]- D-alaninate 1364(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-bromopyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1366(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(5-chloropyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1368(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-fluorobenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1370(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(5-methylpyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1372(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-phenylglycyl-3-[(1-propylbutyl)sulfonyl]- D-alaninate 1374(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}-D-alaninate 1376(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1378(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(1,3-thiazol-4- ylcarbonyl-D-alaninate1380 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(1-acetylpiperidin-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1382(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[4-(acetylamino)butanoyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1384(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-β-3-alanyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1386(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-(chloroacetyl)-3-[(1-propylbutyl)sulfonyl]- D-alaninate 1388(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(methoxyacetyl)-3-[(1-propylbutyl)sulfonyl)-D-alaninate 1390(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-methoxypropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1392(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,2-dimethylpropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1394(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-isobutyryl-3-[(1-propylbutyl)sulfonyl]-D- alaninate 1396(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-butyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1398 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1400 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-[(1-propylbutyl)sulfonyl]-N- (pyridin-3-ylcarbonyl)-D-alaninate 1402(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1404(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1406(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(pyridin-3- ylcarbonyl)-D-alaninate 1408(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1410(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-ethylbenzyl)amino]methyl}propyl N-(cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate 1412(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-propionyl-3-[(1-propylbutyl)sulfonyl]-D- alaninate 1414(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(pyridin-3-ylcarbonyl)alaninate 1416(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1418(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]alaninate 1420(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl3alaninate 1422(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)axnino]methyl}propyl 5-oxo-D-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 1424(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-L-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate 1426(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[3-(4-oxo-2-thioxo-1,3-thiazolidin-3-yl)propanoyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1428(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(piperidin-4-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1430(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1432(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-{[2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]carbonyl}-3-[(1-propylbutyl)sulfonyl]alaninate 1434(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(3,5-dimethylisoxazol-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1436(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1438(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(1H-pyrazol-4- ylcarbonyl)alaninate 1440(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-imidazol-5-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1442(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-imidazol-4-ylacetyl)-3-[(1-proppylbutyl)sulfonyl]alaninate 1444(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(pyrazin-2- ylcarbonyl)alaninate 1446(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6-dihydroxylsonicotinoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1448(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(6-hydroxypyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 1450(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-[(6-chloropyridin-3-yl)carbonyl]-3-[(1- propylbutyl)sulfonyl-alaninate1452 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]alaninate 1454(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(pyridin-3- ylcarbonyl)alaninate 1456(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-ethylbenzyl)amino]methyl}propyl3-[(1-propylbutyl)sulfonyl]-N-(pyridin-2- ylcarbonyl)alaninate 1458(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-indol-6-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride 1460(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(3,4,5-trimethoxybenzoyl)alaninate 1462(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1464(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1466(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1468(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-ethylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1470(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-chlorobenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1472(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[4-(trifluoromethyl)benzoyl]alaninate 1474(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4-methoxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1476(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[4-(trifluoromethyl)benzoyl]alaninate 1478

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(cyclohexylcarbonyl)-3-[(1-propylbutyl) sulfonyl]alaninate 1480

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-benzoyl-3-[(1-propylbutyl)sulfonyl]alaninate 1482

(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propylN-benzoyl-3-[(1-propyl butyl)sulfonyl]alaninate 1484

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1486

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-phenylpro-panoyl)-3-[(1-propylbutyl) sulfonyl]alaninate 1488

(1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(benzoylamino)- 2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 1490

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-phenylpropyl N-(cyclopropylacetyl)-3- [(1-propylbutyl)sulfonyl]alaninate 1492

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-phenylpropyl N-[(methylsulfonyl)acetyl]-3- [(1-propylbutyl)sulfonyl]alaninate 1494

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-phenylpropyl N-[(methylthio)acetyl]-3- [(1 -propylbutyl) sulfonyl]alaninate 1496

1498

(1R,2S)-2-amino-1-{[(3- methoxybenzyl)amino]methyl}-3-phenylpropyl N-[4-(methylamino)-4-oxo butanoyl]-3-[(1-propyl butyl)sulfonyflalaninate1500

1502 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropylN- (methylsulfonyl)glycyl-3-[(1-propylbutyl)sulfonyl]alaninate 1504(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl N-acetyl-3-(phenylsulfonyl)alaninate 1506(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2-[(4-methoxy-4-oxobutanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate 1508(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- {[(benzyloxy)carbonyl]amino}-5-oxo-5-piperidin-1-ylpentanoate1510 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(3-ethoxy-3-oxopropanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate 1512(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl N²-(4-methoxy-4-oxobutanoyl)-N⁵,N⁵-dipropyl-D-glutaminate 1514(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(4-methoxy-4-oxobutanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate 1516(1R,28)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- [(5-methoxy-5-oxoentanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate 1518(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl2-(acetyloxy)-3-(butylsulfonyl)propanoate 1520(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl S-butyl-D-cysteinate 1522(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)aminolmethyl}propyl 3-(butylsulfinyl)-D-alaninate 1524(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-D-alaninate 1526(1R,25-)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-D-alaninate 1528(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(butylsulfonyl)-D-alaninate 1530(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-[(1-propylbutyl)sulfonyl]-D- alaninate 1532(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-L-alaninate1534 (1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl 3-[(1-propylbutyl)sulfonyl]-D-alaninate 1536(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-D-alaninate1538 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-D-alaninate1540 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]alaninate1542 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenoxyacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1544(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propylN-{[(5-chloro-2-thienyl)thio]peroxy}-3-[(1-propylbutyl)sulfonyl]alaninate 1546(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninate 1548(1R,2S)-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}-2-(methylamino)propyl N-[(benzylamino)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate 15504-{[(1R,2S)-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}-2-(methylamino)propyl]oxy}-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoicacid 1552 4-[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]-3-[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoic acid15541-((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl) 4-methyl 2-{[(3-methylbutyl)sulfonyl]methyl}succinate 1556(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 4-amino-2-{[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoate 1558(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 4-(methylamino)-2-[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoate 1560(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 4-(dimethylamino)-2-{[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoate 1562(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 1564(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 1566(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 1568(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-(ethylsulfonyl)-2-{[(isobutylsulfonyl)amino]methyl}propanoate 1570(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-(ethylthio)-2-{[(isobutylsulfonyl)amino]methyl}propanoate 1572(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2- {[(3-methylbutyl)sulfonyl]amino}-4-(methylsulfonyl)butanoate1574 (1R,2S)-2-amino-1-([(3-methoxybenzyl)aminolmethyl}-3-phenylpropylN-[(3- methylbutyl)sulfonyl]-L-methioninate 1576(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 3-(acetylthio)-2-{[(3-methylbutyl)sulfonyl]methyl}propanoate 1578(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl)-3-phenylpropyl 2-hydroxy-3-[(1-propylbutyl)sulfonyl]propanoate 1580(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-hydroxy-3-[(3-methylbutyl)sulfonyl]propanoate 1582(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-hydroxy-3-[(3-methoxyphenyl)sulfonyl]propanoate 1584(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-(phenylsulfonyl)butanoate1586 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl2- hydroxy-4-[(3-methylbutyl)sulfonyl]butanoate 1588(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 4-[(3-methylbutyl)sulfonyl]-2-phenoxybutanoate 1590(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-(3-methoxyphenoxy)-4-[(3-methylbutyl)sulfonyl]butanoate 15923-{1-{[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]carbonyl 1-3-[(3-methylbutyl)sulfonyl]propoxy}benzoicacid 1594 methyl3-{1-{[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoate1596 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl2- hydroxy-4-(phenylsulfonyl)butanoate 1598(1R,2S)-2-amino-1-{[(3-methoxybenzyl)aminolmethyl}-3-phenylpropyl 2-hydroxy-4-(phenylthio)butanoate 1600(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-methoxy-4-(phenylsulfonyl)butanoate 1602(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-methoxy-4-(phenylthio)butanoate 1604(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 4-(phenylsulfonyl)-2-propoxybutanoate 1606(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl 2-(benzyloxy)-4-(phenylsulfonyl)butanoate 1608(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl N-[(benzyloxy)carbonyl]methioninate 1610(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2- amino-5-oxo-5-piperidin-1-ylpentanoate 1612(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2- [(2-methoxy-2-oxoethyl)amino]-5-oxo-5-piperidin-1-ylpentanote1614 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- amino-5-oxo-5-piperidin-1-yllpentanoate 1616(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- [(2-ethoxy-2-oxoethyl)amino]-5-oxo-5-piperidin-1-ylpentanoate1618 (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- [(4-ethoxy-4-oxobutyl)amino]-5-oxo-5-piperidin-1-ylpentanoate1620 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methyl}propyl (2R)-2-[(methoxycarbonyl)amino]-4-oxooctanoate 1622 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl4-butyl-N-(methoxycarbonyl)-D-homoserinate 1624(1R,28)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxolan-2-yl)-N-(methoxycarbonyl)-D-alaninate 1626(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-(methoxycarbonyl)-D-alaninate 1628(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4,4-difluoro-2-[(methoxycarbonyl)amino]octanoate 1630(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-fluoro-2-[(methoxycarbonyl)amino]octanoate 1632(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methyl)}propyl (2R)-2-[(methoxycarbonyl)amino]-5-oxononanoate 1634 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-hydroxy-2-[(methoxycarbonyl)amino]nonanoate 1636(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxolan-2-yl)-2-[(methoxycarbonyl aminolbutanoate 1638(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxan-2-yl)-2-[(methoxycarbonyl)amino]butanoate 1640(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-fluoro-2-[(methoxycarbonyl)amino]nonanoate 1642(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5,5-difluoro-2-[(methoxycarbonyl)amino]nonanoate 1644(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-(methoxycarbonyl)-D- alaninate 1646(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1648(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1650(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate 1652 (1R,2S)-2-amino-3-(3,5-difluorohenyl)-1-[({1-[3-(trifluoromethyl)phenyl-cyclopropyl}amino)methyl]propyl3-(butylsulfonyl)-N- (methoxycarbonyl)-D-alaninate 1654(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol- 5-yl)carbonyl]-D-alaninate1656 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-(butylsulfonyl)-N-[(3-methyl- 1H-pyrazol-5-yl)carbonyl]-D-alaninate1658 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-(butylsulfonyl)-N-[(3-methyl- 1H-pyrazol-5-yl)carbonyl]-D-alaninate1660 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino) methyl)propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D-alaninate 1662(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl)}amino)methyl]propyl3-(butylsulfonyl)-N- [(3-methyl-1H-pyrazol-5-yl)carbonyl]-D-alaninate1664 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-{[(methylamino)carbonyl]amino}-4-oxooctanoate 1666 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-butyl-N-[(methylamino)carbonyl]-D-homoserinate 1668 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxolan-2-yl)-N-[(methylamino)carbonyl]-D-alaninate 1670(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-[(methylamino)carbonyl]-D-alaninate 1672(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4,4-difluoro-2-{[(methylamino)carbonyl]amino}octanoate 1674(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-fluoro-2-{[(methylamino)carbonyl]amino) octanoate 1676(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-{[(methylamino)carbonyl]amino}-5-oxononanoate 1678 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-hydroxy-2- methylaminocarbonyl]amino}nonanoate 1680(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxolan-2-yl)-2-{[(methylamino)carbonyl]amino}butanoate 1682(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxan-2-yl)-2-{[(methylamino)carbonyl]amino}butanoate 1684(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-fluoro-2-{[methylamino)carbonyl]amino}nonanoate 1686(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5,5-difluoro-2-{[(methylamino)carbonyl]amino}nonanoate 1688(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate 1690(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate 1692(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate 1694(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate 1696(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl]propyl3-(butylsulfonyl)-N- [(methylamino)carbonyl]-D-alaninate 1698(1R,28)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol- 1-yl)carbonyl]-D-alaninate1700 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-(butylsulfonyl)-N-[(4-methyl- 1H-pyrazol-1-yl)carbonyl]-D-alaninate1702 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-(butylsulfonyl)-N-[(4-methyl- 1H-pyrazol-1-yl)carbonyl]-D-alaninate1704 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D-alaninate 1706(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl]propyl3-(butylsulfonyl)-N- [(4-methyl-1H-pyrazol-1-yl)carbonyl]-D-alaninate1173

1175

1177

1179

1181

1183

1185

1187

1189

1191

1193

1195

1197

1199

1201

1203

1205

1207

1209

1211

1213

1215

1217

1219

1221

1223

1225

1227

1229

1231

1233 benzyl[(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-(methylsulfonyl)propyl]carbamate 1235

1237

1239

1241

1243

1245

1247

1249

1251

1253

1255

1257

1259

1261

1263

1265

1267

1269

1271

1273

1275

1277

1279

1281

1283

1285

1287

1289

1291

1293

1295

1297

1299 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl)}propyl3-[(1-propylbutyl)sulfonyl]-N-[(tetrahydro-2H-pyran-4-yloxy)carbonyl]alaninate 1301

1303S-(3-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-2-{[(3-methylbutyl)sulfonyl]methyl}-3-oxopropyl) ethanethioate 1305

1307

1309N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-(3-methoxyphenoxy)-4-[(3-methylbutyl)sulfonyl]butanamide 1311

1313

1315

1317

1319

1321

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N¹- (3-ethylbenzyl)-N²-(3,3,3- trifluoropropanoyl)-D-alaninamide 1323

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N¹- (3-ethylbenzyl)-N²- (trifluoroacetyl)-D- alaninamide1325

N-[(2R,3S)-3-amino-2- hydroxy-4-phenylbutyl]- 2-methoxy-N-(3-methoxybenzyl)-4-(phenylthio) butanamide 1327

1329

N¹-[(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2- hydroxybutyl]-3-(butylsulfonyl)-N²- (cyclopropylcarbonyl)- N¹-(3-ethylbenzyl)-D-alaninamide 1331β-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D-alaninamide 1333glycyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-butylsulfonyl)-N¹-(3-ethylbenzyl-D-alaninamide 1335(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2- [(4-ethoxy-4-oxobutyl)amino]-5-oxo-5-piperidin-1-ylpentanoate1337 N,N-dimethyl-β-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl-D-alaninamide 1339N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-N²-(methoxyacetyl)-D-alaninamide 1341

1343

1345 (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-(methoxycarbonyl)-D-alaninate 1347

1349

1351

1353

1355

1357

N²-acetyl-N¹- [(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-3- (butylsulfonyl)-N¹- (3-methylbutyl)-D- alaninamide 1359

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N¹-cyclopropyl-N²- (cyclopropylcarbonyl)-3- [(1-propylbutyl)sulfonyl]-D-alaninamide 1361

N²-acetyl-N¹- [(2R,38)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N¹-(3- methylbutyl)-3-[(1-propylbutyl)sulfonyl]D-alaninamide 1363

1365

1367

1369

1371

1373

N-phenylglycyl-N¹- [(2R,3S)-3-amino-4- (3,5-difluorophenyl)-2-hydroxybutyl}N¹- (3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1375

1377

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1381

1383

1385 N-acetyl-β-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide1387N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(chloroacetyl)-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1389N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(methoxyacetyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide1391 N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(3-methoxypropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1393N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(2,2-dimethylpropanoyl)-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1395N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-isobutyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninamide1397

1399

N²-acetyl-N¹-[(2R,3S) -3-amino-4-(3,5-difluoro phenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3- [(1-propylbutyl)sulfonyl]- D-alaninamide 1401

1403

1405

1407

1409

1411

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N²-(cyclopropylcarbonyl)- N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]D-alaninamide 1413

N¹-[(2R,38)-3-amino-4-(3,5- difluorophenyl)-2- hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-propionyl -3-[(1-propylbutyl)sulfonyl]- D-alaninamide1415

1417

1419

1421

1423

5-oxo-D-prolyl-N¹-[(2R,3S) -3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochloride 1425

5-oxo-L-prolyl-N¹-[(2R,3S) -3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide 1427

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)- N²-[3-(4-oxo-2-thioxo-1,3-thiazolidin-3-yl)propanoyl]- 3-[(1-propylbutyl)sulfonyl]alaninamide 1429

1431

1433

1435

1437

1439

1441

1443

N¹-[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N^(2-(1H-imidazol-4-ylacetyl)- 3-[(1-propylbutyl)sulfonyl]alaninamide)1445

1447

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1451

1453

1455

1457

1459

1461

1463

1465

1467

1469

1471

1473

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1483

1485 N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamide1487 N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninamide1489 N-(3-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-3-oxo-2-{[(1-propylbutyl)sulfonyl]methyl}propyl)benzamide 1491N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N²-(cyclopropylacetyl)-N¹-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide 1493N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylsulfonyl)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamide 1495N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamide 1497

1499

1501

1503N-(methylsulfonyl)glycyl-N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide 1505N²-acetyl-N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-3-(phenylsulfonyl)alaninamide 1507

1509

1511

1513

1515

1517

1519 2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)aminoy]-1-[(butylsulfonyl)methyl]-2-oxoethyl acetate 1521N¹-[(2R,3S)-3-amino-4(3,5-difluorophenyl)-2-hydroxybutyl]-S-butyl-N¹-(3-ethylbenzyl)-D-cysteinamide 1523N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-3-(butylsulfinyl)-N¹-(3-ethylbenzyl)-D-alaninamide 1525N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D-a-aninamide 1527N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-L-alaninamide 1529N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-methylbutyl)-D-alaninamide 1531N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-[1-(3-ethylphenyl)cyclopropyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1533N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-L-alaninamide 1535N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-cyclopropyl-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1537N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-N¹-(3-methylbutyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1539N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide 1541N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide 1543N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenoxyacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamide1545 N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-{[(5-chloro-2-thienyl)thio]peroxy}-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide1547 N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninamide1549N²-[(benzylamino)carbonyl]-N¹-[(2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)butyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide15514-[[(2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)butyl](3-ethylbenzyl)amino]-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoicacid 15534-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-3-{[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoic acid 1555 methyl4-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-3-{[(3-methylbutyl)sulfonyl]methyl}-4-oxobutanoate1557N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-2-{[(3-methylbutyl)sulfonyl)methyl}succinamide 1559N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N⁴-methyl-2-{[(3-methylbutyl)sulfonyl]methyl}succinamide 1561N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N⁴,N⁴-dimethyl-2-{[(3-methylbutyl)sulfonyl]methyl}succinamide 1563N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanamide 1565N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanamide 1567(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-ethylbenzyl)amino]methyl}propyl3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate 1569N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(ethylsulfonyl)-2-{[(isobutylsulfonyl)amino]methyl}-N-(3-methoxybenzyl)propanamide 1571N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(ethylthio)-2-{[(isobutylsulfonyl)amino]methyl}-N-(3-methoxybenzyl)propanamide 1573(2S)-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-{[(3-methylbutyl)sulfonyl]amino}-4-(methylsulfonyl)butanamide 1575N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(3-methylbutyl)sulfonyl]-L-methioninamide 1577S-(3-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-2-{[(3-methylbutyl)sulfonyl]methyl}-3-oxopropyl) ethanethioate 1579N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]propanamide 1581N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N(3-methoxybenzyl)-3-[(3-methylbutyl)sulfonyl]propanamide 1583N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(3-methoxyphenyl)sulfonyl]propanamide 1585N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-(phenylsulfonyl)butanamide 1587N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-[(3-methylbutyl)sulfonyl]butanamide 1589N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-4-[(3-methylbutyl)sulfonyl]-2-phenoxybutanamide 1591N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-(3-methoxyphenoxy)-4-[(3-methylbutyl)sulfonyl]butanamide 15933-{1-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoicacid 1595 methyl 3-{1-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoate1597 N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamide 1599N-[(2R,35-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-(phenylthio)butanamide 1601N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamide 1603N-[(2R,35-3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N-(3-methoxybenzyl)-4-(phenylthio)butanamide 1605N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-4-(phenylsulfonyl)-2-propoxybutanamide 1607N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-(benzyloxy)-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamide 1609

1611

(2S)-2-amino-N-[(2R,3S)- 3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl) -5-oxo-5-piperidin-1- ylpentanamide 1613

1615

(2R)-2-amino-N-[(2R,3S)- 3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl) -5-oxo-5-piperidin-1- ylpentanamide 1617

1619

1621

methyl ((1R)-1-{[[(2R,3S)- 3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-oxoheptyl)carbamate 1623

1625

1627

1629 methyl((1R)-1-{[[(2R,38)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3,3-difluoroheptyl)carbamate 1631 methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-fluoroheptyl)carbamate 1633 methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-oxooctyl)carbamate 1635 methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-hydroxyoctyl)carbamate 1637 methyl[(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-(2-butyl-1,3-dioxolan-2-yl)propyl]carbamate1639 methyl[(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-(2-butyl-1,3-dioxan-2-yl)propyl]carbamate1641 methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-fluorooctyl)carbamate 1643 methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4,4-difluorooctyl)carbamate 1645

1647

1649

1651

1653

1655

1657

1659

1661

1663

1665(2R)-N-((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino}-4-oxooctanamide 1667N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-butyl-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-homoserinamide 1669N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-butyl-1,3-dioxolan-2-yl)-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamide1671N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-butyl-1,3-dioxan-2-yl)-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamide1673(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,4-difluoro-2-{[(methylamino)carbonyl]amino}octanamide1675(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-fluoro-2-{[(methylamino)carbonyl]amino}octanamide 1677(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino 1-5-oxononanamide 1679(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hydroxy-2-{[(methylamino)carbonyl]aminol}nonanamide 1681(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-4-(2-butyl-1,3-dioxolan-2-yl)-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino}butanamide 1683(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2-butyl-1,3-dioxan-2-yl)-N-(3-ethylbenzyl)-2- {[(methylamino)carbonyl]amino}butanamide 1685(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-fluoro-2-{[(methylamino)carbonyl]aminol}nonanamide 1687(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5,5-difluoro-2-[(methylamino)carbonyl]amino}nonanamide 1689N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethynylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamide 1691N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N²-[(methylamino)carbonyl]-N¹-[3-(trifluoromethyl)benzyl]-D-alaninamide1693N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-3-(butylsulfonyl)-N¹-[1-(3-ethylphenyl)cyclopropyl]-N²-[(methylamino)carbonyl]-D-alaninamide1695N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-[1-(3-ethynylphenyl)cyclopropyl]-N²-[(methylamino)carbonyl]-D-alaninamide 1697N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N²-[(methylamino)carbonyl]-N¹-{1-[3-(trifluoromethyl)phenyl]cyclopropyl}-D-alaninamide 1699

1701

1703

1705

1707

1708

1709

1710

1711

1712

1713

1714

1715

1716

1717

1718

1719

1720

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1722

1723

1724

1725

1726

1727

1728

1729

REARRANGEMENT EXAMPLES

[0913] The following examples illustrate the acyl group migration thattakes place with compounds of the invention. These examples are forillustration purposes, and are not intended to limit the scope of theinvention.

[0914] General Procedure:

[0915] A compound of formula (I) OR (X) (5 mg) is dissolved in DMSO-d₆(500 μL) and either pH 4 buffer solution (500 μL, potassium hydrogenphthalate buffer) or pH 7 buffer solution (500 μL, sodium and potassiumphosphate buffer) is added. The sample is then heated to 40° C. TheO-acyl or N-acyl to N-terminal N-acyl migration is monitored byobserving the change in chemical shift for the aromatic fluorines using¹⁹F-NMR. (Fluorine shifts associated with the desired migration wereconfirmed by spiking with authentic analogue). The sample is analyzed by¹⁹F-NMR at approxiamately 0, 1.5, 3, 24, 48, and 144 hours. The amountof O-acyl pro-drug, N-acyl pro-drug, and desired migration product ateach time point are assigned by integrating the corresponding NMRsignal.

Example 1 Specific NMR Example

[0916]

[0917]N˜1˜-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N˜3˜,N˜3˜-dipropyl-N˜1˜-[3-(trifluoromethyl)benzyl]isophthalamidehydrochloride (PREPARATION 7, 5 mg) is dissolved in DMSO-d₆ (500 μL) andpH 4 buffer solution (500 μL, potassium hydrogen phthalate buffer) isadded. The sample is then heated to 40° C. The N-acyl to N-terminalN-acyl migration is monitored by observing the change in chemical shiftfor the aromatic fluorines using ¹⁹F-NMR. (Fluorine shifts for thedesired migration product in the presence of buffer was confirmed byspiking with authentic migration product,N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-(1,3-oxazol-2-yl)-N³,N³-dipropylisophthalamide.)NMR data is collected at 0, 1, 3, 25, 48, 96, and 144 hours. The amountof N-acyl pro-drug and desired migration product present at each timepoint is assigned by integrating the corresponding NMR signal. Nomigration to O-acyl pro-drug was observed using this method and wasconfirmed by spiking with authentic compound.

[0918] The following examples illustrate the solution acyl groupmigration of compounds of the formulae (I) and (X) as observed by ¹⁹FNMR spectroscopy. Data were collected as described in Example 1, above.

Example 2 Rearrangement of(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate (22)

[0919]

[0920] Tables 1-2 provide relative concentrations as a funcation of timeand at varying pH of prodrug 22 and its rearrangement product. TABLE 1Concentrations at 40° C., pH 7. pH 7, 40° C. HEA¹ TIME O-acyl pro-drugN-acyl prodrug product (hr) (% present) (% present) (% present) 0 100 00 0.5 10 0 10 1 0 0 100

[0921] TABLE 2 Concentrations at 40° C., pH 4. pH 4, 40° C. HEA TIMEO-acyl pro-drug N-acyl prodrug product (hr) (% present) (% present) (%present) 0 100 0 0 0.5 93 0 7 1 87 0 13 3 66 0 27 6 49 0 42 24 9 0 78 480 0 86

Example 3 Rearrangement of(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochloride(17)

[0922]

[0923] Tables 3-4 provide relative concentrations as a function of timeand at varying pH of prodrug 17 and its rearrangement product. TABLE 3Concentrations at 40° C., pH 7. pH 7 40° C. HEA TIME O-acyl pro-drugN-acyl prodrug product (hr) (% present) (% present) (% present) 0 100 00 1.5 3 0 97 7 0 24 0 48 0 144 0

[0924] TABLE 4 Concentrations at 40° C., pH 4. pH 4 40° C. HEA TIMEO-acyl pro-drug N-acyl prodrug product (hr) (% present) (% present) (%present) 0 100 0 0 1.5 53 0 47 3 33 0 67 6 11 0 89 24 0 0 100

Example 4 Rearrangement ofN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N\(u)1\(d)-(3-ethylbenzyl)-5-(1,3-oxazol-2-yl)-N³,N³-dispropylisophthalamidehydrochloride (19)

[0925]

[0926] Tables 5-6 provide relative concentrations as a function of timeand at varying pH of prodrug 19 and its rearrangement product. TABLE 5Concentrations at 40° C., pH 7. pH 7 40° C. HEA TIME O-acyl pro-drugN-acyl prodrug product (hr) (% present) (% present) (% present) 0 0 1000 1 0 97 3 3 0 91 9 24 0 60 40 48 0 37 63 96 0 19 81

[0927] TABLE 6 Concentrations at 40° C., pH 4. pH 4 40° C. HEA TIMEO-acyl pro-drug N-acyl prodrug product (hr) (% present) (% present) (%present) 0 0 100 0 1 0 100 0 3 0 100 0 24 0 97 3 48 0 95 5 96 0 92 8

Example 5 Rearrangement ofN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N³,N³-dipropyl-N¹-[3-(trifluoromethyl)benzyl]-isophthalamidehydrochloride (20)

[0928]

[0929] Tables 7-8 provide relative concentrations as a function of timeand at varying pH of prodrug 20 and its rearrangement product. TABLE 7Concentrations at 40° C., pH 7. pH 7 40° C. HEA TIME O-acyl pro-drugN-acyl prodrug product (hr) (% present) (% present) (% present) 0 0 1000 1 0 93 7 3 0 88 12 24 0 49 51 48 0 27 73 96 0 12 88

[0930] TABLE 8 Concentrations at 40° C., pH 4. pH 4 40° C. HEA TIMEO-acyl pro-drug N-acyl prodrug product (hr) (% present) (% present) (%present) 0 0 100 0 1 0 97 3 3 0 96 4 24 0 93 7 48 0 92 8 96 0 88 12

Example 6 Rearrangement of(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl3-[(dispropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochloride(16)

[0931]

[0932] Tables 9-10 provide relative concentrations as a function of timeand at varying pH of prodrug 16 and its rearrangement products. TABLE 9Concentrations at 40° C., pH 7. pH 7 40° C. HEA N-acyl prodrug productTIME O-acyl pro-drug (product A) (product B) (hr) (% present) (%present) (% present) 0 100 0 0 1.5 0 52 48 7 0 46 54 24 0 38 62 48 0 2971 144 0 15 85

[0933] TABLE 10 Concentrations at 40° C., pH 4. pH 4 40° C. HEA N-acylprodrug product TIME O-acyl pro-drug (product A) (product B) (hr) (%present) (% present) (% present) 0 100 0 0 1.5 33 13 54 3 9 15 76 24 012 88 48 0 12 88 144 0 9 91

Example 7 Rearrangement of(1R,2S)-2-amino-3-(3,5-uorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochloride(18)

[0934]

[0935] Tables 11-12 provide relative concentrations as a function oftime and at varying pH of prodrug 18 and its rearrangement products.TABLE 11 Concentrations at 40° C., pH 7. pH 7 40° C. O-acyl N-acylprodrug HEA product TIME pro-drug (product A) (product B) (hr) (%present) (% present) (% present) 0 100 0 0 1.5 0 66 34 7 0 59 41 24 0 4357 48 0 27 73 144 0 16 84

[0936] TABLE 12 Concentrations at 40° C., pH 4. pH 4 40° C. O-acylN-acyl prodrug HEA product TIME pro-drug (product A) (product B) (hr) (%present) (% present) (% present) 0 100 0 0 1.5 32 14 54 3 8 18 74 30 021 79 54 0 20 80 126 0 14 86

BIOLOGY EXAMPLES Example A

[0937] Enzyme Inhibition Assay

[0938] The rearranged compounds of the invention are analyzed forinhibitory activity by use of the MBP-C125 assay. This assay determinesthe relative inhibition of beta-secretase cleavage of a model APPsubstrate, MBP-C125SW, by the compounds assayed as compared with anuntreated control. A detailed description of the assay parameters can befound, for example, in U.S. Pat. No. 5,942,400. Briefly, the substrateis a fusion peptide formed of maltose binding protein (MBP) and thecarboxy terminal 125 amino acids of APP-SW, the Swedish mutation. Thebeta-secretase enzyme is derived from human brain tissue as described inSinha et al, 1999, Nature 40:537-540) or recombinantly produced as thefull-length enzyme (amino acids 1-501), and can be prepared, forexample, from 293 cells expressing the recombinant cDNA, as described inWO00/47618.

[0939] Inhibition of the enzyme is analyzed, for example, by immunoassayof the enzyme's cleavage products. One exemplary ELISA uses an anti-MBPcapture antibody that is deposited on precoated and blocked 96-well highbinding plates, followed by incubation with diluted enzyme reactionsupernatant, incubation with a specific reporter antibody, for example,biotinylated anti-SW192 reporter antibody, and further incubation withstreptavidin/alkaline phosphatase. In the assay, cleavage of the intactMBP-C125SW fusion protein results in the generation of a truncatedamino-terminal fragment, exposing a new SW-192 antibody-positive epitopeat the carboxy terminus. Detection is effected by a fluorescentsubstrate signal on cleavage by the phosphatase. ELISA only detectscleavage following Leu 596 at the substrate's APP-SW 751 mutation site.

[0940] Specific Assay Procedure:

[0941] Compounds are diluted in a 1:1 dilution series to a six-pointconcentration curve (two wells per concentration) in one 96-plate rowper compound tested. Each of the test compounds is prepared in DMSO tomake up a 10 millimolar stock solution. The stock solution is seriallydiluted in DMSO to obtain a final compound concentration of 200micromolar at the high point of a 6-point dilution curve. Ten (10)microliters of each dilution is added to each of two wells on row C of acorresponding V-bottom plate to which 190 microliters of 52 millimolarNaOAc, 7.9% DMSO, pH 4.5 are pre-added. The NaoAc diluted compound plateis spun down to pellet precipitant and 20 microliters/well istransferred to a corresponding flat-bottom plate to which 30 microlitersof ice-cold enzyme-substrate mixture (2.5 microliters MBP-C125SWsubstrate, 0.03 microliters enzyme and 24.5 microliters ice cold 0.09%TX100 per 30 microliters) is added. The final reaction mixture of 200micromolar compound at the highest curve point is in 5% DMSO, 20millimolar NaOAc, 0.06% TX100, at pH 4.5.

[0942] Warming the plates to 37 degrees C. starts the enzyme reaction.After 90 minutes at 37 degrees C., 200 microliters/well cold specimendiluent is added to stop the reaction and 20 microliters/well wastransferred to a corresponding anti-MBP antibody coated ELISA plate forcapture, containing 80 microliters/well specimen diluent. This reactionis incubated overnight at 4 degrees C. and the ELISA is developed thenext day after a 2 hour incubation with anti-192SW antibody, followed byStreptavidin-AP conjugate and fluorescent substrate. The signal is readon a fluorescent plate reader.

[0943] Relative compound inhibition potency is determined by calculatingthe concentration of compound that showed a fifty percent reduction indetected signal (IC₅₀) compared to the enzyme reaction signal in thecontrol wells with no added compound. In this assay, preferred compoundsof the invention exhibit an IC₅₀ of less than 50 micromolar.

Example B

[0944] Cell Free Inhibition Assay Utilizing a Synthetic APP Substrate

[0945] A synthetic APP substrate that can be cleaved by beta-secretaseand having N-terminal biotin and made fluorescent by the covalentattachment of Oregon green at the Cys residue is used to assaybeta-secretase activity in the presence or absence of the inhibitorycompounds of the invention. Useful substrates include the following:Biotin-SEVNL-DAEFRC[oregon green]KK [SEQ ID NO: 1]Biotin-SEVKM-DAEFRC[oregon green]KK [SEQ ID NO: 2]Biotin-GLNIKTEEISEISY-EVEFRC[oregon green]KK [SEQ ID NO: 3]Biotin-ADRGLTTRPGSGLTNIKTEEISEVNL-DAEFRC[oregon green]KK [SEQ ID NO: 4]Biotin-FVNQHLCoxGSHLVEALY-LVCoxGERGFFYTPKAC[oregon green]KK [SEQ ID NO:5]

[0946] The enzyme (0.1 nanomolar) and test compounds (0.001-100micromolar) are incubated in pre-blocked, low affinity, black plates(384 well) at 37 degrees for 30 minutes. The reaction is initiated byaddition of 150 millimolar substrate to a final volume of 30 microliterper well. The final assay conditions are: 0.001-100 micromolar compoundinhibitor; 0.1 molar sodium acetate (pH 4.5); 150 nanomolar substrate;0.1 nanomolar soluble beta-secretase; 0.001% Tween 20, and 2% DMSO. Theassay mixture is incubated for 3 hours at 37 degrees C., and thereaction is terminated by the addition of a saturating concentration ofimmunopure streptavidin. After incubation with streptavidin at roomtemperature for 15 minutes, fluorescence polarization is measured, forexample, using a LJL Acqurest (Ex485 nm/Em530 nm). The activity of thebeta-secretase enzyme is detected by changes in the fluorescencepolarization that occur when the substrate is cleaved by the enzyme.Incubation in the presence or absence of compound inhibitor demonstratesspecific inhibition of beta-secretase enzymatic cleavage of itssynthetic APP substrate. In this assay, preferred compounds of theinvention exhibit an IC₅₀ of less than 50 micromolar.

Example C

[0947] Beta-Secretase Inhibition: P26-P4′SW Assay

[0948] Synthetic substrates containing the beta-secretase cleavage siteof APP are used to assay beta-secretase activity, using the methodsdescribed, for example, in published PCT application WO00/47618. TheP26-P4′SW substrate is a peptide of the sequence:(biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNLDAEF [SEQ ID NO: 6]

[0949] The P26-P1 standard has the sequence:(biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNL. [SEQ ID NO: 7]

[0950] Briefly, the biotin-coupled synthetic substrates are incubated ata concentration of from about 0 to about 200 micromolar in this assay.When testing inhibitory compounds, a substrate concentration of about1.0 micromolar is preferred. Test compounds diluted in DMSO are added tothe reaction mixture, with a final DMSO concentration of 5%. Controlsalso contain a final DMSO concentration of 5%. The concentration of betasecretase enzyme in the reaction is varied, to give productconcentrations with the linear range of the ELISA assay, about 125 to2000 picomolar, after dilution.

[0951] The reaction mixture also includes 20 millimolar sodium acetate,pH 4.5, 0.06% Triton X100, and is incubated at 37 degrees C. for about 1to 3 hours. Samples are then diluted in assay buffer (for example, 145.4nanomolar sodium chloride, 9.51 millimolar sodium phosphate, 7.7millimolar sodium azide, 0.05% Triton X405, 6g/liter bovine serumalbumin, pH 7.4) to quench the reaction, then diluted further forimmunoassay of the cleavage products.

[0952] Cleavage products can be assayed by ELISA. Diluted samples andstandards are incubated in assay plates coated with capture antibody,for example, SW192, for about 24 hours at 4 degrees C. After washing inTTBS buffer (150 millimolar sodium chloride, 25 millimolar Tris, 0.05%Tween 20, pH 7.5), the samples are incubated with streptavidin-APaccording to the manufacturer's instructions. After a one hourincubation at room temperature, the samples are washed in TTBS andincubated with fluorescent substrate solution A (31.2 g/liter2-amino-2-methyl-1-propanol, 30 mg/liter, pH 9.5). Reaction withstreptavidin-alkaline phosphate permits detection by fluorescence.Compounds that are effective inhibitors of beta-secretase activitydemonstrate reduced cleavage of the substrate as compared to a control.

Example D

[0953] Assays Using Synthetic Oligopeptide-Substrates

[0954] Synthetic oligopeptides are prepared that incorporate the knowncleavage site of beta-secretase, and optionally detectable tags, such asfluorescent or chromogenic moieties. Examples of such peptides, as wellas their production and detection methods are described in U.S. Pat. No.5,942,400, herein incorporated by reference. Cleavage products can bedetected using high performance liquid chromatography, or fluorescent orchromogenic detection methods appropriate to the peptide to be detected,according to methods well known in the art.

[0955] By way of example, one such peptide has the sequence SEVNL-DAEF[SEQ ID NO: 8], and the cleavage site is between residues 5 and 6.Another preferred substrate has the sequenceADRGLTTRPGSGLTNIKTEEISEVNL-DAEF [SEQ ID NO: 9], and the cleavage site isbetween residues 26 and 27.

[0956] These synthetic APP substrates are incubated in the presence ofbeta-secretase under conditions sufficient to result in beta-secretasemediated cleavage of the substrate. Comparison of the cleavage resultsin the presence of the compound inhibitor to control results provides ameasure of the compound's inhibitory activity.

Example E

[0957] Inhibition of Beta-Secretase Activity—Cellular Assay

[0958] An exemplary assay for the analysis of inhibition ofbeta-secretase activity utilizes the human embryonic kidney cell lineHEKp293 (ATCC Accession No. CRL-1573) transfected with APP751 containingthe naturally occurring double mutation Lys651Met52 to Asn651Leu652(numbered for APP751), commonly called the Swedish mutation and shown tooverproduce A beta (Citron et al., 1992, Nature 360:672-674), asdescribed in U.S. Pat. No. 5,604,102.

[0959] The cells are incubated in the presence/absence of the inhibitorycompound (diluted in DMSO) at the desired concentration, generally up to10 micrograms/ml. At the end of the treatment period, conditioned mediais analyzed for beta-secretase activity, for example, by analysis ofcleavage fragments. A beta can be analyzed by immunoassay, usingspecific detection antibodies. The enzymatic activity is measured in thepresence and absence of the compound inhibitors to demonstrate specificinhibition of beta-secretase mediated cleavage of APP substrate.

Example F

[0960] Inhibition of Beta-Secretase in Animal Models of AD

[0961] Various animal models can be used to screen for inhibition ofbeta-secretase activity. Examples of animal models useful in theinvention include, but are not limited to, mouse, guinea pig, dog, andthe like. The animals used can be wild type, transgenic, or knockoutmodels. In addition, mammalian models can express mutations in APP, suchas APP695-SW and the like described herein. Examples of transgenicnon-human mammalian models are described in U.S. Pat. Nos. 5,604,102,5,912,410 and 5,811,633.

[0962] PDAPP mice, prepared as described in Games et al., 1995, Nature373:523-527 are useful to analyze in vivo suppression of A beta releasein the presence of putative inhibitory compounds. As described in U.S.Pat. No. 6,191,166, 4 month old PDAPP mice are administered compoundformulated in vehicle, such as corn oil. The mice are dosed withcompound (1-30 mg/ml; preferably 1-10 mg/ml). After time, e.g., 3-10hours, the animals are sacrificed, and brains removed for analysis.

[0963] Transgenic animals are administered an amount of the compoundinhibitor formulated in a carrier suitable for the chosen mode ofadministration. Control animals are untreated, treated with vehicle, ortreated with an inactive compound. Administration can be acute, i.e.,single dose or multiple doses in one day, or can be chronic, i.e.,dosing is repeated daily for a period of days. Beginning at time 0,brain tissue or cerebral fluid is obtained from selected animals andanalyzed for the presence of APP cleavage peptides, including A beta,for example, by immunoassay using specific antibodies for A betadetection. At the end of the test period, animals are sacrificed andbrain tissue or cerebral fluid is analyzed for the presence of A betaand/or beta-amyloid plaques. The tissue is also analyzed for necrosis.

[0964] Animals administered the compound inhibitors of the invention areexpected to demonstrate reduced A beta in brain tissues or cerebralfluids and reduced beta amyloid plaques in brain tissue, as comparedwith non-treated controls.

Example G

[0965] Inhibition of A Beta Production in Human Patients

[0966] Patients suffering from Alzheimer's Disease (AD) demonstrate anincreased amount of A beta in the brain. AD patients are administered anamount of the compound inhibitor formulated in a carrier suitable forthe chosen mode of administration. Administration is repeated daily forthe duration of the test period. Beginning on day 0, cognitive andmemory tests are performed, for example, once per month.

[0967] Patients administered the compound inhibitors are expected todemonstrate slowing or stabilization of disease progression as analyzedby changes in one or more of the following disease parameters: A betapresent in CSF or plasma; brain or hippocampal volume; A beta depositsin the brain; amyloid plaque in the brain; and scores for cognitive andmemory function, as compared with control, non-treated patients.

Example H

[0968] Prevention of a Beta Production in Patients at Risk for AD

[0969] Patients predisposed or at risk for developing AD are identifiedeither by recognition of a familial inheritance pattern, for example,presence of the Swedish Mutation, and/or by monitoring diagnosticparameters. Patients identified as predisposed or at risk for developingAD are administered an amount of the compound inhibitor formulated in acarrier suitable for the chosen mode of administration. Administrationis repeated daily for the duration of the test period. Beginning on day0, cognitive and memory tests are performed, for example, once permonth.

[0970] Patients administered the compound inhibitors are expected todemonstrate slowing or stabilization of disease progression as analyzedby changes in one or more of the following disease parameters: A betapresent in CSF or plasma; brain or hippocampal volume; amyloid plaque inthe brain; and scores for cognitive and memory function, as comparedwith control, non-treated patients.

[0971] The invention has been described with reference to variousspecific and preferred embodiments and techniques. However, it should beunderstood that many variations and modifications may be made whileremaining within the spirit and scope of the invention.

[0972] The invention has been described with reference to variousspecific and preferred embodiments and techniques. However, it should beunderstood that many variations and modifications may be made whileremaining within the spirit and scope of the invention.

What is claimed is:
 1. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein one of R_(N) andR_(N)′ is hydrogen and the other is —C(═O)—(CRR′)₀₋₆R₁₀₀,—C(═O)—(CRR′)₁₋₆—O—R′₁₀₀, —C(═O)—(CRR′)₁₋₆—S—R′₁₀₀,—C(═O)—(CRR′)₁₋₆—C(═O)—R₁₀₀, —C(═O)—(CRR′)₁₋₆—SO₂—R₁₀₀,—C(═O)—(CRR′)₁₋₆—NR₁₀₀—R′₁₀₀, or

wherein R₄ is selected from the group consisting of H; NH₂;—NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; C₁-C₄ alkyl-NHC(O)R₅;—(CH₂)₀₋₄R₈; —O—C₁-C₄ alkanoyl; OH; C₆-C₁₀ aryloxy optionallysubstituted with 1, 2, or 3 groups that are independently halogen, C₁-C₄alkyl, —CO₂H, —C(O)—C₁-C₄ alkoxy, or C₁-C₄ alkoxy; C₁-C₆ alkoxy; arylC₁-C₄ alkoxy; —NR₅₀CO₂R₅₁; —C₁-C₄ alkyl-NR₅₀CO₂R₅₁; —C≡N; —CF₃;—CF₂—CF₃; —C≡CH; —CH₂—CH═CH₂; —(CH₂)₁₋₄—R₄₋₁; —(CH₂)₁₋₄—NH—R₄₋₁;—O—(CH₂)_(n6)—R₄₋₁; —S—(CH₂)_(n6)—R₄₋₁; —(CH₂)₀₋₄—NHC(O)—(CH₂)₀₋₆—R₅₂;—(CH₂)₀₋₄—R₅₃—(CH₂)₀₋₄—R₅₄; wherein n₆ is 0, 1, 2, or 3; n₇ is 0, 1, 2,or 3; R₄₋₁ is selected from the group consisting of —SO₂—(C₁-C₈ alkyl),—SO—(C₁-C₈ alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl),—SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂ alkyl; —CO—NR₄₋₃R₄₋₄; R₄₋₂ and R₄₋₃ areindependently H, C₁-C₃ alkyl, or C₃-C₆ cycloalkyl; R₄₋₄ is alkyl,arylalkyl, alkanoyl, or arylalkanoyl; R₄₋₆ is —H or C₁-C₆ alkyl; R₅ isselected from the group consisting of C₃-C₇ cycloalkyl; C₁-C₆ alkyloptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, —NR₆R₇, C₁-C₄ alkoxy, Cs-C₆ heterocycloalkyl, Cs-C₆ heteroaryl,C₆-C₁₀ aryl, C₃-C₇ cycloalkyl C₁-C₄ alkyl, —S—C₁-C₄ alkyl, —SO₂—C₁-C₄alkyl, —CO₂H, —CONR₆R₇, —CO₂—C₁-C₄ alkyl, C₆-C₁₀ aryloxy; heteroaryloptionally substituted with 1, 2, or 3 groups that are independentlyC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₄ haloalkyl, or OH;heterocycloalkyl optionally substituted with 1, 2, or 3 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, or C₂-C₄ alkanoyl;aryl optionally substituted with 1, 2, 3, or 4 groups that areindependently halogen, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₁-C₄haloalkyl; and —NR₆R₇; wherein R₆ and R₇ are independently selected fromthe group consisting of H, C₁-C₆ alkyl, C₂-C₆ alkanoyl, phenyl,—SO₂—C₁-C₄ alkyl, phenyl C₁-C₄ alkyl; R₈ is selected from the groupconsisting of —SO₂-heteroaryl, —SO₂-aryl, —SO₂-heterocycloalkyl,—SO₂—C₁-C₁₀ alkyl, —C(O)NHR₉, heterocycloalkyl, —S—C₁-C₆ alkyl, —S—C₂-C₄alkanoyl, wherein R₉ is aryl C₁-C₄ alkyl, C₁-C₆ alkyl, or H; R₅₀ is H orC₁-C₆ alkyl; R₅₁ is selected from the group consisting of aryl C₁-C₄alkyl; C₁-C₆ alkyl optionally substituted with 1, 2, or 3 groups thatare independently halogen, cyano, heteroaryl, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇cycloalkyl, or —C₁-C₄ alkoxy; heterocycloalkyl optionally substitutedwith 1 or 2 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, C₂-C₄ alkanoyl, aryl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl;alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3groups that are independently OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); heteroarylalkyloptionally substituted with 1, 2, or 3 groups that are independentlyC₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆alkyl)(C₁-C₆ alkyl); aryl; heterocycloalkyl; C₃-C₈ cycloalkyl; andcycloalkylalkyl; wherein the aryl; heterocycloalkyl, C₃-C₈ cycloalkyl,and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or5 groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy; R₅₂ isheterocycloalkyl, heteroaryl, aryl, cycloalkyl, —S(O)₀₋₂—C₁-C₆ alkyl,CO₂H, —C(O)NH₂, —C(O)NH (alkyl), —C(O)N(alkyl)(alkyl), —CO₂-alkyl,—NHS(O)₀₋₂—C₁-C₆ alkyl, —N(alkyl)S(O)₀₋₂-C₁-C₆ alkyl,—S(O)₀₋₂-heteroaryl, —S(O)₀₋₂-aryl, —NH (arylalkyl),—N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionallysubstituted with 1, 2, 3, 4, or 5 groups that are independently alkyl,alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO₂, CN,alkoxycarbonyl, or aminocarbonyl; R₅₃ is absent, —O—, —C(O)—, —NH—,—N(alkyl)-, —NH—S(O)₀₋₂—, —N(alkyl)-S(O)₀₋₂—, —S(O)₀₋₂—NH—,—S(O)₀₋₂—N(alkyl)-, —NH—C(S)—, or —N(alkyl)-C(S)—; R₅₄ is heteroaryl,aryl, arylalkyl, heterocycloalkyl, CO₂H, —CO₂-alkyl, —C(O)NH(alkyl),—C(O)N(alkyl) (alkyl), —C(O)NH₂, C₁-C₈ alkyl, OH, aryloxy, alkoxy,arylalkoxy, NH₂, NH(alkyl), N(alkyl) (alkyl), or —C₁-C₆ alkyl-CO₂—C₁-C₆alkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5groups that are independently alkyl, alkoxy, CO₂H, —CO₂-alkyl,thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO₂,CN, alkoxycarbonyl, or aminocarbonyl; X is selected from the groupconsisting of —C₁-C₆ alkylidenyl optionally optionally substituted with1, 2, or 3 methyl groups; and —NR₄₋₆—; or R₄ and R₄₋₆ combine to form—(CH₂)_(n10)—, wherein n₁₀ is 1, 2, 3, or 4; Z is selected from thegroup consisting of a bond; SO₂; SO; S; and C(O); Y is selected from thegroup consisting of H; C₁-C₄ haloalkyl; C₅-C₆ heterocycloalkyl; C₆-C₁₀aryl; OH; —N(Y₁)(Y₂); C₁-C₁₀ alkyl optionally substituted with 1 thru 3substituents which can be the same or different and are selected fromthe group consisting of halogen, hydroxy, alkoxy, thioalkoxy, andhaloalkoxy; C₃-C₈ cycloalkyl optionally substituted with 1, 2, or 3groups independently selected from C₁-C₃ alkyl, and halogen; alkoxy;aryl optionally substituted with halogen, alkyl, alkoxy, CN or NO₂;arylalkyl optionally substituted with halogen, alkyl, alkoxy, CN or NO₂;wherein Y₁ and Y₂ are the same or different and are H; C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 substituents selected from thegroup consisting of halogen, C₁-C₄ alkoxy, C₃-C₈ cycloalkyl, and OH;C₂-C₆ alkenyl; C₂-C₆ alkanoyl; phenyl; —SO₂—C₁-C₄ alkyl; phenyl C₁-C₄alkyl; or C₃-C₈ cycloalkyl C₁-C₄ alkyl; or Y₁, Y₂ and the nitrogen towhich they are attached form a ring selected from the group consistingof piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein eachring is optionally substituted with 1, 2, 3, or 4 groups that areindependently C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy C₁-C₆ alkyl, orhalogen; R₁ is —(CH₂)₁₂—S(O)₀₋₂—(C₁-C₆ alkyl), or C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom halogen, OH, ═O, —SH, —C≡N, —CF₃, —C₁-C₃ alkoxy, amino, mono- ordialkylamino, —N(R)C(O)R′—, —OC(═O)-amino and —OC(═O)-mono- ordialkylamino, or C₂-C₆ alkenyl or C₂-C₆ alkynyl, each of which isoptionally substituted with 1, 2, or 3 groups independently selectedfrom halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, and mono- ordialkylamino, or aryl, heteroaryl, heterocyclyl, —C₁-C₆ alkyl-aryl,—C₁-C₆ alkyl-heteroaryl, or —C₁-C₆ alkyl-heterocyclyl, where the ringportions of each are optionally substituted with 1, 2, 3, or 4 groupsindependently selected from halogen, —OH, —SH, —C≡N, —NR₁₀₅R′₁₀₅, —CO₂R,—N(R)COR′, or —N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono ordialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino,—SO₂—(C₁-C₄)alkyl, or —C₁-C₆ alkoxy optionally substituted with 1, 2, or3 groups which are independently a halogen, or C₃-C₇ cycloalkyloptionally substituted with 1, 2, or 3 groups independently selectedfrom halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, —C₁-C₆ alkyland mono- or dialkylamino, or C₁-C₁₀ alkyl optionally substituted with1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N,—CF₃, —C₁-C₃ alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, orC₂-C₁₀ alkenyl or C₂-C₁₀ alkynyl each of which is optionally substitutedwith 1, 2, or 3 groups independently selected from halogen, —OH, —SH,—C≡N, —CF₃, C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- or dialkylamino;and the heterocyclyl group is optionally further substituted with oxo; Rand R′ independently are hydrogen or C₁-C₁₀ alkyl; R₂ is selected fromthe group consisting of H; C₁-C₆ alkyl, optionally substituted with 1,2, or 3 substituents that are independently selected from the groupconsisting of C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,and —NR_(1-a)R_(1-b); wherein R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl;—(CH₂)₀₋₄-aryl; —(CH₂)₀₋₄-heteroaryl; C₂-C₆ alkenyl; C₂-C₆ alkynyl;—CONR_(N-2)R_(N-3); —SO₂NR_(N-2)R_(N-3); —CO₂H; and —CO₂—(C₁-C₄ alkyl);R₃ is selected from the group consisting of H; C₁-C₆ alkyl, optionallysubstituted with 1, 2, or 3 substituents independently selected from thegroup consisting of C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃alkoxy, and —NR_(1-a)R_(1-b); —(CH₂)₀₋₄-aryl; —(CH₂)₀₋₄-heteroaryl;C₂-C₆ alkenyl; C₂-C₆ alkynyl; —CO—NR_(N-2)R_(N-3); —SO₂—NR_(N-2)R_(N-3);—CO₂H; and —CO—O—(C₁-C₄ alkyl); or R₂, R₃ and the carbon to which theyare attached form a carbocycle of three thru seven carbon atoms, whereinone carbon atom is optionally replaced by a group selected from-O—, —S—,—SO₂—, or —NR_(N-2)—; R_(C) is selected from the group consisting ofC₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 groups independentlyselected from the group consisting of R₂₀₅, —OC═ONR₂₃₅R₂₄₀,—S(═O)₀₋₂(C₁-C₆ alkyl), —SH, —NR₂₃₅C═ONR₂₃₅R₂₄₀, —C═ONR₂₃₅R₂₄₀, and—S(═O)₂NR₂₃₅R₂₄₀; —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl wherein the cycloalkyl isoptionally substituted with 1, 2, or 3 groups independently selectedfrom the group consisting of R₂₀₅, —CO₂H, and —CO₂—(C₁-C₄ alkyl);—(CR₂₄₅R₂₅₀)₀₋₄-aryl; —(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl; —(CR₂₄₅R₂₅₀)₀₋₄-aryl-heteroaryl;(CR₂₄₅R₂₅₀)₀₋₄-aryl-heterocycloalkyl; —(CR₂₄₅R₂₅₀)₀₋₄-aryl-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-aryl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-heteroaryl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-heterocycloalkyl;—(CR₂₄₅R₂₅₀)₀₋₄-heterocycloalkyl-aryl; —[C(R₂₅₅) (R₂₆₀)]₁₃—CO—N—(R₂₅₅)₂;—CH(aryl)₂; —CH(heteroaryl)₂; —CH(heterocycloalkyl)₂; —CH(aryl)(heteroaryl); cyclopentyl, cyclohexyl, or cycloheptyl ring fused toaryl, heteroaryl, or heterocycloalkyl wherein one carbon of thecyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with NH,NR₂₁₅, O, or S(═O)₀₋₂, and wherein the cyclopentyl, cyclohexyl, orcycloheptyl group can be optionally substituted with 1 or 2 groups thatare independently R₂₀₅ or ═O; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); C₂-C₁₀alkenyl optionally substituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₁₀alkynyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—(CH₂)₀₋₁—CH((CH₂)₀₋₆—OH)—(CH₂)₀₋₁-aryl;—(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-heteroaryl; —CH(-aryl or-heteroaryl)-CO—O(C₁-C₄ alkyl); —CH(—CH₂—OH)—CH(OH)-phenyl-NO₂; (C₁-C₆alkyl)-O—(C₁-C₆ alkyl)-OH; —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂; —H; and—(CH₂)₀₋₆—C(═NR₂₃₅) (NR₂₃₅R₂₄₀); wherein each aryl is optionallysubstituted with 1, 2, or 3 R₂₀₀; each heteroaryl is optionallysubstituted with 1, 2, 3, or 4 R₂₀₀; each heterocycloalkyl is optionallysubstituted with 1, 2, 3, or 4 R₂₁₀; R₂₀₀ at each occurrence isindependently selected from the group consisting of C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; OH; —NO₂; halogen;—CO₂H; C≡N; —(CH₂)₀₋₄—CO—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl);—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl); —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl);—(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl); —(CH₂)₀₋₄—CO-aryl;—(CH₂)₀₋₄—CO-heteroaryl; —(CH₂)₀₋₄—CO-heterocycloalkyl;—(CH₂)₀₋₄—CO₂R₂₁₅; —(CH₂)₀₋₄—SO₂—NR₂₂₀R₂₂₅; —(CH₂)₀₋₄—SO—(C₁-C₅ alkyl);—(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl); —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl);—(CH₂)₀₋₄—N(H or R₂₁₅)—CO₂R₂₁₅; —(CH₂)₀₋₄—N(H or R₂₁₅)—CO—N(R₂₁₅)₂;—(CH₂)₀₋₄—N—CS—N(R₂₁₅)₂; —(CH₂)₀₋₄—N (—H or R₂₁₅)—CO—R₂₂₀;—(CH₂)₀₋₄—NR₂₂OR₂₂₅; —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl);—(CH₂)₀₋₄—O—P(O)—(OR₂₄₀)₂; —(CH₂)₀₋₄—O—CO—N(R₂₁₅)₂;—(CH₂)₀₋₄—O—CS—N(R₂₁₅)₂; —(CH₂)₀₋₄—O—(R₂₁₅)₂; —(CH₂)₀₋₄—O—(R₂₁₅)₂—COOH;—(CH₂)₀₋₄—S—(R₂₁₅)₂—(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with1, 2, 3, or 5-F); C₃-C₇ cycloalkyl; C₂-C₆ alkenyl optionally substitutedwith 1 or 2 R₂₀₅ groups; C₂-C₆ alkynyl optionally substituted with 1 or2 R₂₀₅ groups; —(CH₂)₀₋₄—N(H or R₂₁₅)—SO₂—R₂₂₀; and —(CH₂)₀₋₄—C₃-C₇cycloalkyl; wherein each aryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀ orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀; wherein each heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 groups that are independentlyR₂₁₀; wherein each heteroaryl group at each occurrence is optionallysubstituted with 1, 2, or 3 groups that are independently R₂₀₅, R₂₁₀, orC₁-C₆ alkyl substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀; R₂₀₅ at each occurrence is independently selected from thegroup consisting of C₁-C₆ alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N,—CF₃, C₁-C₆ alkoxy, NH₂, NH (C₁-C₆ alkyl), and N-(C₁-C₆ alkyl)(C₁-C₆alkyl); R₂₁₀ at each occurrence is independently selected from the groupconsisting of C₁-C₆ alkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; C₂-C₆ alkenyl optionally substituted with 1, 2, or 3 R₂₀₅groups; C₂-C₆ alkynyl optionally substituted with 1, 2, or 3 R₂₀₅groups; halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; —NR₂₂₀R₂₂₅; OH; C≡N;C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅ groups;—CO—(C₁-C₄ alkyl); SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and═O; wherein R₂₁₅ at each occurrence is independently selected from thegroup consisting of C₁-C₆ alkyl, —(CH₂)₀₋₂-(aryl), C₂-C₆ alkenyl, C₂-C₆alkynyl, C₃-C₇ cycloalkyl, and —(CH₂)₀₋₂-(heteroaryl),—(CH₂)₀₋₂-(heterocycloalkyl); wherein the aryl group at each occurrenceis optionally substituted with 1, 2, or 3 groups that are independentlyR₂₀₅ or R₂₁₀; wherein the heterocycloalkyl group at each occurrence isoptionally substituted with 1, 2, or 3 R₂₁₀; wherein each heteroarylgroup at each occurrence is optionally substituted with 1, 2, or 3 R₂₁₀;R₂₂₀ and R₂₂₅ at each occurrence are independently selected from thegroup consisting of —H, —C₁-C₆ alkyl, hydroxy C₁-C₆ alkyl, amino C₁-C₆alkyl; halo C₁-C₆ alkyl; —C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇cycloalkyl), —(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl), —C₂-C₆ alkenyl, —C₂-C₆alkynyl, —C₁-C₆ alkyl chain with one double bond and one triple bond,-aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group ateach occurrence is optionally substituted with 1, 2, or 3 R₂₇₀ groups,wherein R₂₇₀ at each occurrence is independently R₂₀₅, C₁-C₆ alkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkenyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkynyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; halogen; C₁-C₆alkoxy; C₁-C₆ haloalkoxy; NR₂₃₅R₂₄₀; OH; C≡N; C₃-C₇ cycloalkyloptionally substituted with 1, 2, or 3 R₂₀₅ groups; —CO—(C₁-C₄ alkyl);SO₂NR₂₃₅R₂₄₀; —CO—NR₂₃₅R₂₄₀; —SO₂—(C₁-C₄ alkyl); and ═O; wherein theheterocycloalkyl group at each occurrence is optionally substituted with1, 2, or 3 R₂₀₅ groups; wherein each heteroaryl group at each occurrenceis optionally substituted with 1, 2, or 3 R₂₀₅ groups; R₂₃₅ and R₂₄₀ ateach occurrence are independently H, or C₁-C₆ alkyl; R₂₄₅ and R₂₅₀ ateach occurrence are independently selected from the group consisting ofH, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, aryl C₁-C₄alkyl, heteroaryl C₁-C₄ alkyl, and phenyl; or R₂₄₅ and R₂₅₀ are takentogether with the carbon to which they are attached to form a carbocycleof 3, 4, 5, 6, or 7 carbon atoms, optionally where one carbon atom isreplaced by a heteroatom selected from the group consisting of —O—, —S—,—SO₂—, and —NR₂₂₀—; R₂₅₅ and R₂₆₀ at each occurrence are independentlyselected from the group consisting of H; C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkenyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; C₂-C₆ alkynyl optionallysubstituted with 1, 2, or 3 R₂₀₅ groups; —(CH₂)₁₂—S(O)₀₋₂—(C₁-C₆ alkyl);—(CH₂)₀₋₄—C₃-C₇ cycloalkyl optionally substituted with 1, 2, or 3 R₂₀₅groups; —(C₁-C₄ alkyl)-aryl; —(C₁-C₄ alkyl)-heteroaryl; —(C₁-C₄alkyl)-heterocycloalkyl; -aryl; -heteroaryl; -heterocycloalkyl;(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-aryl; —(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heteroaryl; and;—(CH₂)₁₋₄—R₂₆₅—(CH₂)₀₋₄-heterocycloalkyl; wherein R₂₆₅ at eachoccurrence is independently —O—, —S— or —N(C₁-C₆ alkyl)-; each aryl orphenyl is optionally substituted with 1, 2, or 3 groups that areindependently R₂₀₅, R₂₁₀, or C₁-C₆ alkyl substituted with 1, 2, or 3groups that are independently R₂₀₅ or R₂₁₀; each heteroaryl isoptionally substituted with 1, 2, 3, or 4 R₂₀₀, each heterocycloalkyl isoptionally substituted with 1, 2, 3, or 4 R₂₁₀; R₁₀₀ and R′₁₀₀independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl,-aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl,-heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl,-heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl,-heterocyclyl-W-heterocyclyl, —CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-aryl,—CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-heterocyclyl or—CH[(CH₂)₀₋₂—O—R₁₅₀]—(CH₂)₀₋₂-heteroaryl, where the ring portions ofeach are optionally substituted with 1, 2, or 3 groups independentlyselected from —OR, —NO₂, C₁-C₆ alkyl, halogen, —C≡N, —OCF₃, —CF₃,—(CH₂)₀₋₄—O—P(═O)(OR)(OR₁), —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—(CH₂)₀₋₄—CONR₁₀₂R₁₀₂′, —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),—(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl), —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl),—(CH₂)₀₋₄—CO—(CH₂)₀₋₄(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀,—(CH₂)₀₋₄—R₁₃₀, —(CH₂)₀₋₄—CO—R₁₁₀, —(CH₂)₀₋₄—CO—R₁₂₀, —(CH₂)₀₋₄—CO—R₁₃₀,—(CH₂)₀₋₄—CO—R₁₄₀, —(CH₂)₀₋₄—CO—O—R₁₅₀, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₅₀,—(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), —(CH₂)₀₋₄—SO₂ (C₁-C₁₂ alkyl),—(CH₂)₀₋₄—SO₂—(CH₂)₀₋₄—(C₃-C₇ cycloalkyl), —(CH₂)₀₋₄—N(R₁₅₀)—CO—O—R₁₅₀,—(CH₂)₀₋₄—N(R₁₅₀)—CO—N(R₁₅₀)₂, —(CH₂) O₄—N(R₁₅₀)—CS—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—CO—R₁₀₅, —(CH₂)₀₋₄—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—R₁₄₀,—(CH₂)₀₋₄—CO—(C₁-C₆ alkyl), —(CH₂)₀₋₄—O—P(O)—(O—R₁₁₀)₂,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—CS—N(R₁₅₀)₂, —(CH₂)₀₋₄—O—(R₁₅₀),—(CH₂)₀₋₄—O—R₁₅₀′—COOH, —(CH₂)₀₋₄—S—(R₁₅₀), —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C₂-C₁₀)alkenyl, and (C₂-C₁₀)alkynyl, orR₁₀₀ is C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3 R₁₁₅ groups,or R₁₀₀ is —(C₁-C₆ alkyl)-O—C₁-C₆ alkyl) or —(C₁-C₆ alkyl)-S—(C₁-C₆alkyl), each of which is optionally substituted with 1, 2, or 3 R₁₁₅groups, or R₁₀₀ is C₃-C₈ cycloalkyl optionally substituted with 1, 2, or3 R₁₁₅ groups; W is —(CH₂)₀₋₄—, —O—, —S(O)₀₋₂, —N(R₁₃₅)—, —CR(OH)— or—C(O)—; R₁₀₂ and R₁₀₂′ independently are hydrogen, or C₁-C₁₀ alkyloptionally substituted with 1, 2, or 3 groups that are independentlyhalogen, aryl or —R₁₁₀; R₁₀₅ and R′₁₀₅ independently represent —H,—R₁₁₀, —R₁₂₀, C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl),—(C₁-C₆ alkyl)-O—(C₁-C₃ alkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆alkyl chain with one double bond and one triple bond, or C₁-C₆ alkyloptionally substituted with —OH or —NH₂; or, C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,or R₁₀₅ and R′₁₀₅ together with the atom to which they are attached forma 3 to 7 membered carbocylic ring, where one member is optionally aheteratom selected from —O—, —S(O)₀₋₂—, —N(R₁₃₅)—, the ring beingoptionally substituted with 1, 2 or 3 independently selected R₁₄₀groups; R₁₁₅ at each occurrence is independently halogen, —OH, —CO₂R₁₀₂,—C₁-C₆ thioalkoxy, —CO₂-phenyl, —NR₁₀₅R′₁₃₅, —SO₂—(C₁-C₈ alkyl),—C(═O)R₁₈₀, R₁₈₀, —CONR₁₀₅R′₁₀₅, —SO₂NR₁₀₅R′₁₀₅, —NH—CO—(C₁-C₆ alkyl),—NH—C(═O)—OH, —NH—C(═O)—OR, —NH—C(═O)—O-phenyl, —O—C(═O)—(C₁-C₆ alkyl),—O—C(═O)-amino, —O—C(═O)-mono- or dialkylamino, —O—C(═O)-phenyl,—O—(C₁-C₆ alkyl)-CO₂H, —NH—SO₂—(C₁-C₆ alkyl), C₁-C₆ alkoxy or C₁-C₆haloalkoxy; R₁₃₅ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₇cycloalkyl, —(CH₂)₀₋₂-(aryl), —(CH₂)₀₋₂-(heteroaryl), or—(CH₂)₀₋₂—(heterocyclyl); R₁₄₀ is heterocyclyl optionally substitutedwith 1, 2, 3, or 4 groups independently selected from C₁-C₆ alkyl, C₁-C₆alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C₁-C₆)alkylamino,di(C₁-C₆)alkylamino, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl,C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino(C₁-C₆)alkyl,di(C₁-C₆)alkylamino(C₁-C₆)alkyl, and ═O; R₁₄₅ is C₁-C₆ alkyl or CF₃;R₁₅₀ is hydrogen, C₃-C₇ cycloalkyl, —(C₁-C₂ alkyl)-(C₃-C₇ cycloalkyl),C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one double bond and onetriple bond, —R₁₁₀, —R₁₂₀, or C₁-C₆ alkyl optionally substituted with 1,2, 3, or 4 groups independently selected from —OH, —NH₂, C₁-C₃ alkoxy,R₁₁₀, and halogen; R₁₅₀′ is C₃-C₇ cycloalkyl, —(C₁-C₃ alkyl)-(C₃-C₇cycloalkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkyl with one doublebond and one triple bond, —R₁₁₀, —R₁₂₀, or C₁-C₆ alkyl optionallysubstituted with 1, 2, 3, or 4 groups independently selected from —OH,—NH₂, C₁-C₃ alkoxy, R₁₁₀, and halogen; R₁₅₅ is C₃-C₇ cycloalkyl, —(C₁-C₂alkyl)-(C₃-C₇ cycloalkyl), C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkylwith one double bond and one triple bond, —R₁₁₀, —R₁₂₀, or C₁-C₆ alkyloptionally substituted with 1, 2, 3, or 4 groups independently selectedfrom —OH, —NH₂, C₁-C₃ alkoxy, and halogen; R₁₈₀ is selected frommorpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl,homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinylS,S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionallysubstituted with 1, 2, 3, or 4 groups independently selected from C₁-C₆alkyl, C₁-C₆ alkoxy, halogen, hydroxy, cyano, nitro, amino,mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, amino(C₁-C₆)alkyl, mono(C₁-C₆)alkylamino (C₁-C₆)alkyl, di(C₁-C₆)alkylamino (C₁-C₆)alkyl, and═O; R₁₁₀ is aryl optionally substituted with 1 or 2 R₁₂₅ groups; R₁₂₅ ateach occurrence is independently halogen, amino, mono- or dialkylamino,—OH, —C≡N, —SO₂—NH₂, —SO₂—NH—C₁-C₆ alkyl, —SO₂—N(C₁-C₆ alkyl)₂,—SO₂—(C₁-C₄ alkyl), —CO—NH₂, —CO—NH—C₁-C₆ alkyl, or —CO—N(C₁-C₆ alkyl)₂,or C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl, each of which isoptionally substituted with 1, 2, or 3 groups that are independentlyselected from C₁-C₃ alkyl, halogen, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,amino, and mono- and dialkylamino, or C₁-C₆ alkoxy optionallysubstituted with one, two or three of halogen; R₁₂₀ is heteroaryl, whichis optionally substituted with 1 or 2 R₁₂₅ groups; and R₁₃₀ isheterocyclyl optionally substituted with 1 or 2 R₁₂₅ groups.
 2. Acompound according to claim 1 wherein R_(N) is hydrogen.
 3. A compoundaccording to claim 1 wherein R_(N)′ is hydrogen.
 4. A compound accordingto claim 1 wherein R₁ is —C₁-C₆ alkyl-aryl, —C₁-C₆ alkyl-heteroaryl, or—C₁-C₆ alkyl-heterocyclyl, where the ring portions of each areoptionally substituted with 1, 2, 3, or 4 groups independently selectedfrom halogen, —OH, —SH, —C≡N, —NO₂, —NR₁₀₅R′₁₀₅, —CO₂R, —N(R)COR′, or—N(R)SO₂R′, —C(═O)—(C₁-C₄)alkyl, —SO₂-amino, —SO₂-mono or dialkylamino,—C(═O)-amino, —C(═O)-mono or dialkylamino, —SO₂—(C₁-C₄) alkyl, or C₁-C₆alkoxy optionally substituted with 1, 2, or 3 groups which areindependently selected from halogen, or C₃-C₇ cycloalkyl optionallysubstituted with 1, 2, or 3 groups independently selected from halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, amino, —C₁-C₆ alkyl and mono- ordialkylamino, or C₁-C₁₀ alkyl optionally substituted with 1, 2, or 3groups independently selected from halogen, —OH, —SH, —C≡N, —CF₃, —C₁-C₃alkoxy, amino, mono- or dialkylamino and —C₁-C₃ alkyl, or C₂-C₁₀ alkenylor C₂-C₁₀ alkynyl each of which is optionally substituted with 1, 2, or3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, amino, C₁-C₆ alkyl and mono- or dialkylamino; and theheterocyclyl group is optionally further substituted with oxo.
 5. Acompound according to claim 1 wherein R₂ and R₃ are independentlyselected from H or C₁-C₆ alkyl optionally substituted with 1, 2, or 3substituents selected from the group consisting of C₁-C₃ alkyl, halogen,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a R) _(1-b).
 6. Acompound according to claim 1 wherein R_(C) is —(CR₂₄₅R₂₅₀)₀₋₄-aryl, or—(CR₂₄₅R₂₅₀)₀₋₄-heteroaryl, wherein aryl and heteroaryl are optionallysubstituted with 1, 2, or 3 R₂₀₀ groups.
 7. A compound according toclaim 2 wherein R_(N)′ is

wherein R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or—NR₅₀CO₂R₅₁; wherein n₆ is 0, 1, 2, or 3; n₇ is 0, 1, 2, or 3; R₄₋₁ isselected from the group consisting of —SO₂—(C₁-C₈ alkyl), —SO—(C₁-C₈alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl), —SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂alkyl; —CO—NR₄₋₃R₄₋₄; R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, orC₃-C₆ cycloalkyl; R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, orphenylalkanoyl; R₅ is cyclopropyl; cyclobutyl; cyclopentyl; andcyclohexyl; wherein each cycloalkyl group is optionally substituted withone or two groups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl,C₁-C₆ alkoxy, more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆alkyl), N(C₁-C₆ alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or thecycloalkyl group is substituted with 1 or 2 groups that areindependently CF₃, Cl, F, methyl, ethyl or cyano; C₁-C₆ alkyl optionallysubstituted with 1, 2, or 3 groups that are independently halogen,—NR₆R₇, C₁-C₄ alkoxy, C₅-C₆ heterocycloalkyl, C₅-C₆ heteroaryl, phenyl,C₃-C₇ cycloalkyl, —S—C₁-C₄ alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇,—CO₂—C₁-C₄ alkyl, or phenyloxy; heteroaryl optionally substituted with1, 2, or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, C₁-C₄ haloalkyl, or OH; heterocycloalkyl optionally substitutedwith 1, 2, or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, or C₂-C₄ alkanoyl; phenyl optionally substituted with 1, 2, 3,or 4 groups that are independently halogen, OH, C₁-C₄ alkyl, C₁-C₄alkoxy, or C₁-C₄ haloalkyl; and —NR₆R₇; wherein R₆ and R₇ areindependently selected from the group consisting of H, C₁-C₆ alkyl,C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenyl C₁-C₄ alkyl; R₈ isselected from the group consisting of —SO₂-heteroaryl optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl orhalogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉, heterocycloalkyl,—S—C₂-C₄ alkanoyl, wherein R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H;R₅₀ is H or C₁-C₆ alkyl; R₅, is selected from the group consisting ofphenyl C₁-C₄ alkyl; C₁-C₆ alkyl optionally substituted with 1, 2, or 3groups that are independently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇or —C₁-C₄ alkoxy; heterocycloalkyl optionally substituted with 1 or 2groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄alkanoyl, phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl;heterocycloalkylalkyl optionally substituted with 1 or 2 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenylC₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryloptionally substituted with 1, 2, or 3 groups that are independently OH,C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆alkyl)(C₁-C₆ alkyl); heteroarylalkyl optionally substituted with 1, 2,or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl,and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or5 groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy.
 8. A compoundaccording to claim 3 wherein R_(N) is

wherein R₄ is NH₂; —NH—(CH₂)_(n6)—R₄₋₁; —NHR₈; —NR₅₀C(O)R₅; or—NR₅₀CO₂R₅₁; wherein n₆ is 0, 1, 2, or 3; n₇ is 0, 1, 2, or 3; R₄₋₁ isselected from the group consisting of —SO₂—(C₁-C₈ alkyl), —SO—(CL-C₈alkyl), —S—(C₁-C₈ alkyl), —S—CO—(C₁-C₆ alkyl), —SO₂—NR₄₋₂R₄₋₃; —CO—C₁-C₂alkyl; —CO—NR₄₋₃R₄₋₄; R₄₋₂ and R₄₋₃ are independently H, C₁-C₃ alkyl, orC₃-C₆ cycloalkyl; R₄₋₄ is alkyl, phenylalkyl, C₂-C₄ alkanoyl, orphenylalkanoyl; R₅ is cyclopropyl; cyclobutyl; cyclopentyl; andcyclohexyl; wherein each cycloalkyl group is optionally substituted withone or two groups that are C₁-C₆ alkyl, more preferably C₁-C₂ alkyl,C₁-C₆ alkoxy, more preferably C₁-C₂ alkoxy, CF₃, OH, NH₂, NH(C₁-C₆alkyl), N(C₁-C₆ alkyl)(C₁-C₆ alkyl), halogen, CN, or NO₂; or thecycloalkyl group is substituted with 1 or 2 groups that areindependently CF₃, Cl, F, methyl, ethyl or cyano; CL-C₆ alkyl optionallysubstituted with 1, 2, or 3 groups that are independently halogen,—NR₆R₇, C₁-C₄ alkoxy, C₅-C₆ heterocycloalkyl, C₅-C₆ heteroaryl, phenyl,C₃-C₇ cycloalkyl, —S—C₁-C₄ alkyl, —SO₂—C₁-C₄ alkyl, —CO₂H, —CONR₆R₇,—CO₂—C₁-C₄ alkyl, or phenyloxy; heteroaryl optionally substituted with1, 2, or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, C₁-C₄ haloalkyl, or OH; heterocycloalkyl optionally substitutedwith 1, 2, or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy,halogen, or C₂-C₄ alkanoyl; phenyl optionally substituted with 1, 2, 3,or 4 groups that are independently halogen, OH, C₁-C₄ alkyl, C₁-C₄alkoxy, or C₁-C₄ haloalkyl; and —NR₆R₇; wherein R₆ and R₇ areindependently selected from the group consisting of H, C₁-C₆ alkyl,C₂-C₆ alkanoyl, phenyl, —SO₂—C₁-C₄ alkyl, and phenyl C₁-C₄ alkyl; R₈ isselected from the group consisting of —SO₂-heteroaryl optionallysubstituted with 1 or 2 groups that are independently C₁-C₄ alkyl orhalogen;, —SO₂-aryl, —SO₂-heterocycloalkyl, —C(O)NHR₉, heterocycloalkyl,—S—C₂-C₄ alkanoyl, wherein R₉ is phenyl C₁-C₄ alkyl, C₁-C₆ alkyl, or H;R₅₀ is H or C₁-C₆ alkyl; R₅₁ is selected from the group consisting ofphenyl C₁-C₄ alkyl; C₁-C₆ alkyl optionally substituted with 1, 2, or 3groups that are independently halogen, cyano, —NR₆R₇, —C(O)NR₆R₇, C₃-C₇or —C₁-C₄ alkoxy; heterocycloalkyl optionally substituted with 1 or 2groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄alkanoyl, phenyl C₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl;heterocycloalkylalkyl optionally substituted with 1 or 2 groups that areindependently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, C₂-C₄ alkanoyl, phenylC₁-C₄ alkyl, and —SO₂ C₁-C₄ alkyl; alkenyl; alkynyl; heteroaryloptionally substituted with 1, 2, or 3 groups that are independently OH,C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen, NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆alkyl)(C₁-C₆ alkyl); heteroarylalkyl optionally substituted with 1, 2,or 3 groups that are independently C₁-C₄ alkyl, C₁-C₄ alkoxy, halogen,NH₂, NH(C₁-C₆ alkyl) or N(C₁-C₆ alkyl)(C₁-C₆ alkyl); phenyl; C₃-C₈cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C₃-C₈ cycloalkyl,and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or5 groups that are independently halogen, CN, NO₂, C₁-C₆ alkyl, C₁-C₆alkoxy, C₂-C₆ alkanoyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, hydroxy,C₁-C₆ hydroxyalkyl, C₁-C₆ alkoxy C₁-C₆ alkyl, C₁-C₆ thioalkoxy, C₁-C₆thioalkoxy C₁-C₆ alkyl, or C₁-C₆ alkoxy C₁-C₆ alkoxy.
 9. A compoundaccording to claim 2 wherein R_(N)′ is —C(═O)-phenyl, where the phenylring is optionally substituted with 1 or 2 groups independently selectedfrom C₁-C₆ alkyl, halogen, —(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅,—(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂, —(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅,—(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₀₅, C₃-C₇ cycloalkyl, (C₂-C₁₀) alkenyl,—(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or (C₂-C₁₀) alkynyl. 10.A compound according to claim 3 wherein R_(N) is —C(═O)-phenyl, wherethe phenyl ring is optionally substituted with 1 or 2 groupsindependently selected from C₁-C₆ alkyl, halogen,—(CH₂)₀₋₄—CO—NR₁₀₅R′₁₀₅, —(CH₂)₀₋₄—O—CO—N(R₁₅₀)₂,—(CH₂)₀₋₄—N(R₁₅₀)—SO₂—R₁₀₅, —(CH₂)₀₋₄—SO₂—NR₁₀₅R′₁₁₅, C₃-C₇ cycloalkyl,(C₂-C₁₀)alkenyl, —(CH₂)₀₋₄—R₁₁₀, —(CH₂)₀₋₄—R₁₂₀, —(CH₂)₀₋₄—R₁₃₀, or(C₂-C₁₀) alkynyl.
 11. A compound according to claim 1 selected from thegroup consisting of: N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D- alaninamidedihydrochioride N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl[-D-alaninamide trifluoroacetateN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamide hydrochlorideN-[(2R,3S)-3-amirio-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(methylsulfonyl)amino]-1,3-thiazole-5-carboxamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-L-alaninamide bis(trifluoroacetate)N-[(2R,3S)-3-amino-4-(3,5-ditluorophenyl)2 hydroxybutyl]-3-(butylsulfonyl)-N-(3- ethylbenzyl)propanamide hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)1{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)propanoatedihydrochioride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochioride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3- ethylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochioride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl[amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate dihydrochlorideN¹-[(2R, 3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-N\(u)1\(d)-(3-ethylbenzyl)-5-(1,3-oxazol-2-yl)-N³,N³-dipropylisophthalamide hydrochlorideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N³,N³-dipropyl-N¹-[3-(trifluoromethyl)benzyl]isophthalamide hydrochlorideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N³,N³-dipropyl-N₁-[3-(trifluoromethyl)benzyl]isophthalamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoateN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-N²[(methoxy)carbonyl]-D-alaninamide dihydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(2-hydroxyethyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}methyl)propyl 3- [(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-isopropylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-l-{[(3-isopropylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(4-methyl-1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2-isobutyl-l,3-thiazol-5-yl)methyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(3-hydroxypropyl)amino]sulfonyl}benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-propylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(methyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-{[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(3-isobutylisoxazol-5-yl)methyl]aminolmethyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(5-formyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[(1R)-2-hydroxy-1-methylethyl]amino}sulfonyl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)1{[(3isobutylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzoate hydrochloride(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[(1S)-2-hydroxy-1-methylethyl]amino}sulfonyl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(propyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dibutylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-hydroxyprop-1-yn-1-yl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{butyl(ethyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[cyclohexyl(methyl)amino]carbonyl)-5-methylbenzoate(1R,2S)-2-amino-1-({[3- (cyclopropylamino)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-thienyl)benzyl]amino}methyl) propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(piperazin-1-ylsulfonyl)benzoate dihydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-iodophenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-sec-butylbenzyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(3-methylisoxazol-4-yl)benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,sdifluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[(dipropylamino)carbonyl]-6-methylisonicotinate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{](cyclopropylmethyl)(propyl)amino]carbonyl}-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(aminosulfonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(1Z)-prop-1-en-1-yl]benzyl)amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1H-pyrazol-4-yl)benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-1-{[(3-allylbenzyl)amino]methyl}-2-amino-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3- {[ethyl(propyl)amino]carbonyl}-5-methylbenzoate (1R,2S)-2-amino-]- ({[3-(cyclopropylamino)benzyl]amino}methyl)-3-(3,5- difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynyiphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(5-formyl-4-methyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-isopropylbenzyl)amino]methyl}propyl 5-[(dipropylamino)carbonyl]nicotinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(methylsulfonyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 3-[(butylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-methylbutyl)benzyl]amino)methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(biphenyl-3-ylmethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-({[2-(methylamino)ethyl]amino}sulfonyl)benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-isobutylisoxazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-ethynylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diallylamino)carbonyl]-5-methylbenzoate (1R,2R)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(2-isobutyl-1,3-thiazol-5-yl)cyclopropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2- hydroxyethyl)amino]sulfonyl}-5-[(propylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(propyl)amino]carbonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diethylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzylamino)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate trifluoroacetate(1R,2S)-2-amino-3-(3,5-difluorophenylyl{](3-pyridin- 3-ylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]- 5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3ethylbenzyl)amino]methyl}propyl 5- [(dipropylamino)carbonyl]nicotinate1-oxide (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3-formyl-2-furyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-(1-methyl-1H-imidazol-2-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diethylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(ethylsulfinyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[butyl(ethyl)amino]sulfonyl}propanoate(1R,2S)-2-amino-1-{[(3-cyanobenzyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1- propylbutyl)sulfonyl]propanoatehydrochloride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[isobutyl(methyl)amino]carbonyl)-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[3-pyridin-2-ylbenzyl)amino[methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[methyl(methylsultonyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninate trifluoroacetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3- (ethylsulfonyl)benzyl]amino}methyl) propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-chloro-2-thienyl)sulfonyl]-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride(1R,2S)-1-({[3-(5-acetyl-2- thienyl)benzyl]amino}methyl)-2-amino-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(secbutylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1,3-oxazol-2-yl)benzoatehydrochloride (1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino[methyl}propyl 3-methyl-5-{]methyl(2-phenylethyl)amino]carbonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(3,5-dimethylisoxazol-4-yl0)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(prop-2-yn-l-yl)amino[carbonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[ethyl(methyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-{[(dimethylamino)carbonyl]oxy}benzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[benzyl(methyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[secbutyl(propyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(4-methyl-2-thienyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(methoxycarbonyl)(methyl)amino]benzyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-1-({[3-(trifluoromethyl)benzyl]amino}methyl)-3-(2,3,5- trifluorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diisobutylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-5-{[methyl(2-pyridin-2-ylethyl)amino)carbonyl}benzoate(1R,2S)-2-amino-3-(3-fluoro-5-hydroxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate hydrochloride(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}proptl 5-oxo-D-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-pyridin-4-ylbenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-[({3-[(dimethylamiflo)sulfonyl]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino]methy}propyl 3-([dipropylamiflo)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(azepan-1-ylcarbonyl)-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-[({3-[(methoxycarboflyl)amino]benzyl}amino)methyl]propyl 3-[(dipropylamiflo)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-L-prolyl-3-[(1-propylbutyl)sulfonyl]alafliflate hydrochloride(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(isobutylamino)carbonyl]-5-methylbenzoate 4-[((1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl)oxyl-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoic acid trifluoroacetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3- [methyl(methylsulfonyl)amino]benzoateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(2-hydroxyethyl)amino])sulfonyl}-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[(2-isobutyl-1,3-thiazol-5-yl)methyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-(3-isopropylbenzyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isopropylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(4-methyl-1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2-isobutyl-1,3-thiazol-5-yl)methyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(3-hydroxypropyl)amino]sulfonyl}-N′,N′-dipropylisophthalamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3- propylbenzyl)isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-N′,5- dimethylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-(3-ethynylbenzyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[(3-isobutylisoxazol-5-yl)methyl]-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-[(dimethylamino)sulfonyl]-N-(3-ethylbenzyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-(5-forrnyl-2-thienyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-bromo-N-(3-iodobenzyl)-N[,N]- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[(1R)-2-hydroxy-1-methylethyl]amino}sulfonyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isobutylbenzyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)berizyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[(1S)-2-hydroxy-1-methylethyl]amino}sulfonyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-dibutyl-N-(3-ethylbenzyl)-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(3-hydroxyprop-1-yn-1-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl}-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethynylbenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-cyclohexyl-N-(3-ethylbenzyl)-N′,5-dimethylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(cyclopropylamino)benzyl]-5-ethynyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-[3-(3-thienyl)benzyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(piperazin-1-ylsulfonyl)-N′,N′-dipropylisophthalamide dihydrochiorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-sec-butylbenzyl)-5-methyl-N′,N′- dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(3-methylisoxazol-4-yl)-N′,N′-dipropylisophthalamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-isobutylisoxazol-s-yl)cyclopropyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)cyclopropyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN⁴-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N4-(3-ethylbenzyl)-6-methyl-N²-N²-dipropylpyridine-2,4-dicarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(cyclopropylmethyl)-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamideN-(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-aminc-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethynylphenyyl)cyclopropyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamldeN-[(2R,3S)-3-amino-4-(3,5-difluoropheflyl)-2-hydroxybutyl]-5-(aminosulfonyl)-N-(3-ethylbenzyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-[(1Z)-prop-1-en-1-yl]benzyl}-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylphenyl)-N′,N′-dipropyl-5-(1H-pyrazol-4-yl)isophthalamide hydrochorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-ethynyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamideN-(3-allylbenzyl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)cyclopropyl]-5-methyl-N′,N′dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-(1,3-oxazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(cyclopropylamino)benzyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethyryl-N-[1-(3-ethynylphenyl)cyclopropyl]-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-diflurophenyl)-2-hydroxybutyl]-N-[1-(3-isobutylisoxazol-5-yl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamideN-(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-(5-formyl-4-methyl-2-thienyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-isopropylbenzyl)-N′,N′-dipropylpyridine-3,5-dicarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3-[(methylsulfonyl)amano]benzyl}-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-butyl-N-(3-ethylbenzyl)-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(3-methylbutyl)benzyl]-N′,N′-dapropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluoropheflyl)-2-hydroxybutyl]-N-(biphenyl-3-ylmethyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethynylphenyl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-({[2-(methylamino)ethyl]amino}sulfonyl)-N′,N′- dipropylisophthalamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-ethynyl-N-[1-(3-isobutylisoxazol-5-yl)cyclopropyl]-N′,N′-dipropylisophthalamideN,N-diallyl-N′-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3-ethylbenzyl)-5-methylisophthalamideN-[(2R,3R)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(2-isobutyl-1,3-thiazol-5-yl)cyclopropyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(3-ethylphenyl)-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-{{[(2-hydroxyethyl)amino]sulfonyl}-N′-propylisophthalamideN-[(2R,38)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′- propylisophthalamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-diethyl-N-(3-ethylbenzyl)-5-(1,3-oxazol-2-yl)isophthalamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-[(benzylamino)carbonyl]-N¹-(3-ethylbenzyl) -3-[(1-propylbutyl)sulfonyl]alaninamide trifluoroacetate (salt)N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3-pyridin-3-ylbenzyl)isophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-dipropylpyridine-3,5-dicarboxamide 1-oxide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-[3-(3-formyl-2-furyl)benzyl]-5-methyl-N′-propylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1-methyl-1H-imidazol-2-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′,N′-diethyl-N-(3-ethylbenzyl)-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(ethylsulfinyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-{[butyl(ethyl)amino]sulfonyl}-N-(3-ethylbenzyl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-cyanoberizyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(1- propylbutyl)sulfonyl]propanamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isobutyl-N′,5- dimethylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3-pyridin-2-ylbenzyl)isophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-iodobenzyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3- [methyl(methylsulfonyl)amino]benzyl]-N′,N′-dipropylisophthalamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N2-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninamide trifluoroacetate (salt)N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(ethylsulfonyl)benzyl]-5-methyl-N′,N′-dipropylisophthalamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-[(5-chloro-2-thienyl)sulfonyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochlorideN-[3-(5-acetyl-2-thienyl)benzyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(sec-butyl)-N-(3-ethylbenzyl)-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1,3-oxazol-2-yl)benzamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-(2-phenylethyl)isophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(3,5-dimethylisoxazol-4-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,s-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-prop-2-yn-1-ylisophthalamide N-[(2R,3S)-3-amino-4-(3,s-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-N′,5- dimethylisophthalamide3-[([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5- methylbenzoyl}amino)methyl]phenyl dimethylcarbamateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-benzyl-N-(3-ethylbenzyl)-N′,5- dimethylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(sec-butyl)-N-(3-ethylbenzyl)-5-methyl-N′-propylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(4-methyl-2-thienyl)benzyl]-N′,N′-dipropylisophthalamidemethyl{3-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)methyl]phenyl}methylcarbamateN-[(2R,3S)-3-amino-2-hydroxy-4-(2,3,5-trifluorophenyl)butyl]-5-methyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-diisobutyl-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,5-dimethyl-N′-(2-pyridin-2-ylethyl)isophthalamideN-[(2R,3S)-3-amino-4-(3-fluoro-5-hydroxyphenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′- dipropylisophthalamidehydrochloride N¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-hydroxy-N-(3-iodobenzyl)-3-(pyrrolidin-1-ylcarbonyl)benzamide 5-oxo-D-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N^(1-(3-ethylbenzyl)-3-[(1-)propylbutyl)sulfonyl]alaninamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropyl-N-(3-pyridin-4-ylbenzyl)isophthalamide N-′(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{3-[(dimethylamino)sulfonyl]benzyl}-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-5-methyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(azepan-1-ylcarbonyl)-N-(3-ethylbenzyl)-5-methylbenzamide methyl{3-[([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)methyl]phenyl}carbamate 5-oxo-L-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isobutyl-5- methylisophthalamide4-[[(2R, 3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-4-oxo-3-{[(1-propylbutyl)sultonyl]methyl}butanoic acid trifluoroacetate (salt)N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[methyl(methylsulfonyl)amino]benzamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[ethyl(isopropyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- (2-thienyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[isopropyl(methyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[allyl(cyclopentyl)amino]carbonyl)-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3- methylbutyl)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(5-methyl-2-thienyl)benzyl]amino}methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methoxyphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-methylhexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoale (1R,2S)-2-amino-1-({[1-(aminocarbonyl)cyclohexyl]amino}methyl)-3-(3,5- difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2E)-hex-2-en-1-ylamino]methyl}propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(4-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-hydroxyisoxazole-5- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[(1E)-hex-1-en-1-yl]benzyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(isopropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- (2-thienyl) propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [3-(2-amino-2- oxoethoxy)phenyl]acetate(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-ethyihexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(6-methoxypyridin-3-yl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(2,4-dimethoxypyrimidin-5-yl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-ethylbutanoyl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-[2′- (aminocarbonyl)biphenyl-4-yl]-4-oxobutanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-hydroxy-1-phenylpropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[[2-(dimethylamino)ethyl](ethyl)amino]carbonyl}-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(5-acetyl-2-thienyl)acetate(1R,2S)-2-amino-3-(3,5-dichiorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(diisopropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3- [(methylsulfonyl)amino]benzoate(1R,2S)-2-amino-3-(4-chiorophenyl)-1-{[(3-methoxybenzyl)amino]methyllpropyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [4-(2-oxopyrrolidin-1- yl)phenyl]acetate(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{](3- methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}benzoate trihydrochioride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1- [(pentylamino)methyl]propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(4-fluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-chloro-5-fluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{{[3-ethylbenzyl)amino]methyl}propyl 3-{]cyclohexyl(ethyl)amino]carbonyl)-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-({[(2,4-difluorophenyl)amino]carbonyl}oxy)ethyl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl)-5-methylbenzoate hydrochloride(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2, 8-dimethylquinoline-3- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(6-hydroxyhexyl)amino]methyl}propyl 3-](dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2R)-2-hydroxypropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-[(1-propylbutyl)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(4-phenylbutyl)amino]methyl}propyl 3[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 7-(1H-imidazol-1-yl)-5,6-dihydronaphthaiene-2 -carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(acetylamino)-4- methylbenzoate(1R,2S)-2-amino-1-({[2- (aminosulfonyl)ethyl[amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-(ethylthio)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-cyclohexyl-1-{[(3- methoxybenzyl)amino]methyl}propyl3- [(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[benzyl(cyanomethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-hydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-butoxypropyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[2-(2-hydroxyethyl)piperidin-1-yl]carbonyl}-5-methyibenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1-hydroxy-2- propylpentyl)benzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-chloro-5-fluorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4- [(methylsulfonyl)amino]butanoatetrifluoroacetate (1R,2S)-2-amino-1-({[3-(1-benzothien-2-yl)benzyl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(benzyloxy)isoxazole-5- carboxylate(1R,2S)-2-amino-1-55 [(cyclopropylmethyl)amino]methyl}-3-(3,5-difiuorophenyl)propyl N-{(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl}alaninate trifluoroacetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(1H-pyrazol-1 yl)pentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1-(2-furylmethyl)-5-oxopyrrolidine-3-carboxylate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-ethylhexanoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(5-hydroxypentyl)amino]methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]piperidine-1-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(diethylamino)carbonyl]piperidine-1-carboxylate(1R,2S)-2-amino-3-(pentafluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4- [(methylsulfonyl)amino]benzoate(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methya}-3- (2-thienyl)propyl3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethoxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2s)-2-amino-1-[(benzylamino)methyl]-3-(2- thienyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4- (phenylsulfonyl)butanoatehydrochloride (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-ethyl-N-(3-ethylbenzyl)-N′-isopropyl-5-methylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isopropyl-N′, 5-dimethylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamideN-allyl-N′-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-cyclopentyl-N′-(3-ethylbenzyl)-5- methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(3- methylbutyl)sulfonyl]propanamideN-[(2R,3S)-3-arnino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[3-(5-methyl-2-thienyl)benzyl]-N′,N′-dipropylisophthalamide N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(1-methyihexyl)-N′,N′- dipropylisophthalamideN-[1-(aminocarbonyl)cyclohexyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2E)-hex-2-en-l-yl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-hydroxyisoxazole-5- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{3-[(1E)-hex-1-en-1-yl]benzyl}-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-isopropyl-5- methylisophthalamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide2-(3-{2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-iodobenzyl)amino]-2- oxoethyl}phenoxy)acetamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-ethyihexyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(6-methoxypyridin-3-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluoropheriyl)-2-hydroxybutyl]-N-[3-(2,4-dimethoxypyrimidin-5-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluoropheriyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-ethylbutancyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamideN¹-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N′-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5- tricarboxamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 4-[2′-(aminocarbonyl)biphenyl-4-yl]-4-oxobutanoate1-(3-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-5-methylbenzoyl)-L-prolinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-hydroxy-1-phenylpropyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-[2-(dimethylamino)ethyl]-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine-4-carboxamide2-(5-acetyl-2-thienyl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)acetamideN¹-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′,N′-diisopropyl-5-methylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3- [(methylsulfonyl)amino]benzamideN¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-iodobenzyl)-2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetamide N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)suitonyl]-N-(3-methoxybenzyl)propanamideN¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}benzamide trihydrochiorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-pentyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-cyclohexyl-N′-ethyl-N-(3-ethylbenzyl)-5-methylisophthalamide 2-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)ethyl(2,4-difluorophenyl)carbamateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl)-5-methylbenzamide hydrochlorideN¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN¹-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluoropheflyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,8-dimethylquinoline-3- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(6-hydroxyhexyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2R)-2-hydroxypropyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2-hydroxy-1,1-dimethylethyl)amino]sulfonyl}benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(4-phenylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-7-(1H-imidazol-1-yl)-N-(3-iodobenzyl)-5,6-dihydronaphthalene-2-carboxamide3-(acetylamino)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4- methylbenzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[2-(aminosulfonyl)ethyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[2-(ethylthio)ethyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-hydroxypropyl)-5-methyl-N′,N′- dipropylisophthalamideN-′(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-butoxypropyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[2-(2-hydroxyethyl)piperidin-1-yl]carbonyl}-5-methylbenzamide methylN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}-β-alaninate N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1-hydroxy-2- propylpentyl)benzamideN¹-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4- [(methylsulfonyl)amino]butanamidetrifluoroacetate (salt) N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(1-benzothien-2-yl)benzyl]-5-methyl-N′,N′-dipropylisophthalamideN-′(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(benzyloxy)-N-(3-ethylbenzyl)isoxazole-5- carboxamide1-(3-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-5-methylbenzoyl)-D-prolinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(1H-pyrazol-1 yl)pentanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1-(2-furylmethyl)-5-oxopyrrolidine-3-carboxamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-ethyl-N-(3-methoxybenzyl)hexanamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(5-hydroxypentyl)-5-methyl-N′,N′- dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylpiperidine-1,3-dicarboxamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N³,N³-diethyl-N¹-(3-methoxybenzyl)piperidine-1,3-dicarboxamide N-[(2R,3S)-3-amino-2-hydroxy-4-(pentafluorophenyl)butyl]-5-bromo-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4- [(methylsulfonyl)amino]benzamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethoxypropyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4- (phenylsulfonyl)butanamidehydrochloride N¹-[(2R,3S)-3-amino-4-(3,5-dichiorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3,3-dimethylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3- bromophenyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1,3-diphenyipropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-1(hydroxyrnethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(3S)-2-oxoazepan-3-yl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(cyclohexylamino)-5- oxopentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-propylpentyl)sulfonyl]-β-alaninate trifluoroacetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1,3-thiazol-2-yl)benzoatdihydrochioride (1R,2S)-2-amino-3-(2-furyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({3-[methyl(phenyl)amino]propyl}amino)methyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-1-(2-thienylmethyl)pyrrolidine-3-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(butylthio)methyl]-5-methyl-2-furoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylberizyl)amino]methyl}propyl 3-{[(2-hydroxyethyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[3- (trifluoromethyl)benzoyl]glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylcyclohexyl)amino]methyl}propyl 3-[(diprapylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-oxo-1,3-oxazolidin-3- yl)benzoate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-pyrrol-1-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1,3,4,5-tetrahydrothiopyrano[4,3-b]indole-8-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[2-(trifluoromethyl)phenyl]amino)butanoate(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4,5-dimethyl-2-(1H-pyrrol-1-yl)thiophene-3-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2,3-dihydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(2S)-2-hydroxypropyl]amino)methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-1-methyipropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-chloro-4- (methylsulfonyl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-hydroxyethyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methoxyphenyl)propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl 3-{methyl[(trifluoromethyl)suifonyl]amino}benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl 3-hydroxy-6-(1-hydroxy-2,2-dimethyipropyl)pyridine-2-carboxylate (1R,2S)-2-amino-1-{[(1,3-dicyclohexylpropyl)amino]methyl}-3-(3,5- difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,2′-bithiophene-5- carboxylate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-imidazol-1- yl)butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,3-dihydroxy-4-[(4-methoxyphenyl)amino]-4-oxobutanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4- hydroxyphenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2- thienyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-({[2-(aminocarbonyl)-1H-indol-6-yl]amino}methyl)-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3- bromophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[4- (trifluoromethyl)benzoyl]glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3,4- dichlorobenzoyl)glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-chloro-4-(methylsulfonyl)thiophene-2-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-ethylpropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({[(5R)-3-ethyl-2-oxo-1,3-oxazolidin-s-yl]methyl}amino)methyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxylate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(methylthio)acetyl]-3-[(1- propylbutyl)sulfonyl]alaninatehydrochloride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2,3-dimethylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4, 5-dimethoxy-1-benzothiophene-2-carboxylate(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-s-yl]methyllamino)methyl]propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,5-dioxo-1,2,4-triazolidin-4-yl)benzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl2-hydroxy-3- [(3- methoxyphenyl)sulfonyl]propanoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(2-methylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-{](2-{4-[(3-chlorobenzyl)oxy]phenyl}ethyl)amino]methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-(3- thienyl)butanoate(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-[3-(trifluoromethyl)phenyl]butanoate(1R,2S)-2-amino-1-{](3-methylbutyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)-3-(methylthio)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylberizoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1H-1,2,3-benzotriazol-1- yl)hexanoate(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{](1- propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-{[(trifluoromethyl)sulfonyl]amino}butanoate trifluoroacetate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-hydroxypropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3,5- dichiorophenyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-{[(2- hydroxyethyl)(propyl)amino]sulfonyl}propanoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(benzylthio)nicotinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-pyrazole-5-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-chloro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-benzimidazole-2- carboxylate(1R,2S)-2-amino-3-cyclohexyl-1-{[(3- methoxybenzyl)amino]methyl}propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-hydroxy-4,7-dimethoxy-1-benzofuran-5-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(4-methylcyclohexyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [1,2,4]triazolo[4,3-a]pyridine-6-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-oxo-4-(2- thienyl)butanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3,5- dichiorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 4-(2-hydroxy-5-methylphenyl)-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-phenoxybenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4- [(aminocarbonyl)amino]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-1-(hydroxymethyl)-3-(methylthio)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 7-hydroxy-4-oxochromane-2- carboxylate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-({[(1S)-1-(hydroxymethyl)-3-methylbutyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-1-(hydroxymethyl)propyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(1-methyl-3-phenyipropyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3,3-dimethylbutyl)-5-methyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(1,3-diphenylpropyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-1-(hydroxymethyl)propyl]-N′,N′-dipropylisophthalamide N-[(2R,35)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[(3S)-2-oxoazepan-3-yl]-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-cyclohexyl-N-(3-ethylbenzyl)pentanediamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N³-[(2-propylpentyl)sulfonyl]-β-alaninamide trifluoroacetate (salt)N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1,3-thiazol-2- yl)benzamidedihydrochloride N-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-{3-[methyl(phenyl)amino]propyl}-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-oxo-1-(2-thienylmethyl)pyrrolidine-3-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-[(butylthio)methyl]-N-(3-ethylbenzyl)-5-methyl-2-furamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{[(2-hydroxyethyl)amino]sulfonyl}benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylcyclohexyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-oxo-1,3-oxazolidin-3- yl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-pyrrol-1-yl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1,3,4,5-tetrahydrothiopyrano[4,3-b]indole-8-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-[2-(trifluoromethyl)phenyl]succinamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N[,N]-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,5-dimethyl-2-(1H-pyrrol-1-yl)thiophene-3-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2,3-dihydroxypropyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(2S)-2-hydroxypropyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[(1R)-1-methylpropyl]-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-chloro-N-(3-ethylbenzyl)-4- (methylsulfonyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-hydroxyethyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{methyl[(trifluoromethyl)sulfonyl]amino}benzamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-hydroxy-6-(1-hydroxy-2,2-dimethylpropyl)pyridine-2-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(1,3-dicyclohexylpropyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,2′-bithiophene-5- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-imidazol-1- yl)butanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dihydroxy-N′-(4-methoxyphenyl)succinamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N′-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[2-(aminocarbonyl)-1H-indol-6-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-chloro-N-(3-ethylbenzyl)-4-(methylsulfonyl)thiophene-2-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(1-ethylpropyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{[(5R)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2,3-dimethylcyclohexyl)-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,5-dimethoxy-1-benzothiophene-2-carboxamide N¹-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl[-2-hydroxybutyl}-N¹-(3-methylbutyl)-N₃,N₃-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-5-methyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,5-dioxo-1,2,4-triazolidin4-yl)-N-(3-ethylbenzyl)benzamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(3-methoxyphenyl) sulfonyl]propanamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(2-methylcyclohexyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(2-{4-[(3-chlorobenzyl)oxy]phenyl}ethyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-(3- thienyl)butanamideN¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-N¹- (3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-(3-methylbutyl)-N³,N³⁻dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(hydroxymethyl)-3-(methylthio)propyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1H-1,2,3-benzotriazol-1-yl-N-(3- ethylbenzyl)hexanamideN¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-{[(trifluoromethyl)sulfonyl]amino}butanamide trifluoroacetate (salt)N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-hydroxypropyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[1-(hydroxymethyl)propyl]-5-methyl-N′,N′-dipropylisophthalamide N¹-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(2-hydroxyethyl)(propyl)amino]sulfonyl}-N-(3- methoxybenzyl)propanamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-ditluorophenyl)-2-hydroxybutyl]-5-(benzylthio)-N-(3-ethylbenzyl)nicotinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-pyrazole-5-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethylbenzyl)-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-benzimidazole-2- carboxamideN¹-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyly)-2-hydroxybutyl]-N-(3-ethylbenzyl)-6-hydroxy-4,7-dimethoxy-1-benzofuran-5-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(4-methylcyclohexyl)-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-oxo-4-(2- thienyl)butanamideN-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-hydroxy-5-methylphenyl)-4-oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-phenoxybenzamide4-[(aminocarbonyl)amino]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-1-(hydroxymethyl)-3-(methylthio)propyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-7-hydroxy-4-oxochromane-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)propyl]-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-(1-methyl-3-phenylpropyl)-N′,N′-dipropylisophthalamide (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxylate(1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-oxo-3- (pentylamino)propanoate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(trifluoromethoxy)benzoate(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methoxybenzyl)amino)methyl}propyl 3- (dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3-methyibutyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-{[4- (acetylamino)phenyl]methyl}propyl(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1-cyanoethy)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]butanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethoxy)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-(2-oxo-2-pyrrolidin-1-ylethoxy)phenyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (1,1-dioxidotetrahydro-2-thienyl)acetate (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-chlorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3ethylbenzyl)amino]methyl}propyl 5-hex-1-yn-1-ylnicotinate(1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methoxyisoxazole-5- carboxylate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,3-dimethyl-1H-indole-7- carboxylate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-chlorophenyl)-2-hydroxy-4-oxobutanoate(1R,2S)-2-amino-3-(3-fluoro-4-methoxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (1-methyl-1H-indol-3- yl)(oxo)acetate(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methylphenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-fluoro-4-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [5-(4-methylphenyl)-2H-tetrazol-2-yl]acetate (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(2- thienyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl[benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methyl-3-phenylisoxazole-4-carboxylate (1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(methylsulfonyl)acetyl]-N-pentylglycinate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4- methoxybenzoyl)glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6- difluorobenzoyl)glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1H-indol-3-yl)-4- oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(5-benzyl-1,3,4-thiadiazol-2-yl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-fluoro-4-methoxyphenyl)-4-oxobutanoate ethyl4-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}oxy)butyl]amino}piperidine-1-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-fluorobenzoyl)-1H-pyrrole-2-carboxylate (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4-chlorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]berizoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(4-hydroxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (4-morpholin-4- ylphenyl)acetate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[benzyl(1-cyclopropylethyl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(2,5-dimethylbenzoyl)-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(2-methoxy-5-methylphenyl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(3-hydroxyphenyl)acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[hydroxy(2-methylphenyl)methyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(ethylthion)nicotinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[4-(2-furoyl)piperazin-1-yl]-5-oxobutanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-fluoro-4-methylphenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-oxoisoindoline-1- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino[methyl}propyl 3-(ethylthio)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl thieno[2,3-b]quinoline-2- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl 3-(4-methyl-1,3-oxazo1-2- yl)benzoatehydrochloride (1R,2S)-2-amino-1-[(benzylamino)methyl)-3-(4-fluorophenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethyibenzyi)amino]methyl]propyl 2-[2- furoyl(methyl)amino]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-(3-methoxyphenyl)-4-oxobutanoate(1R,2S)-2-amino-1-[(cycloheptylamino)methyl}-3-(3,5-difluorophenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(4-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3-fluoro-s-hydroxyphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoatehydrochloride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-hydroxy-1H-indole-2- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,2-dimethylchromane-8- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-benzylpyrazine-2- carboxylate 4-oxide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl {2-[(dipropylamino)sulfonyl]ethyl}carbamate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(hydroxymethyl)-2-methylpropyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2s)-2-amino-1-[(benzylamino)methyl]-3-(3-chloro-5-fluorophenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-methoxyphenyl)-4- oxobutanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4- hydroxyphenyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-4-oxo-3,4-dihydrophthalazine-1-carboxylate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3,4-dihydro-2H-1,5-benzodioxepine-7-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [4-(2,5-dioxopyrrolidin-1-yl)phenoxy]acetate (1R,2S)-2-amino-3-(2-furyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3- (aminocarbonyl) -5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl) -5-[(dipropylamino)carbonyl]benzoate (1R,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-{[(3- methoxybenzyl)amino]methyl}propyl5-(dipropylamino)-5- oxopentanoate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1{[(3-ethylbenzyl)amino]methyl}propyl 6-fluoro-2-hydroxyquinoline-4-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-(2-thienyl)butanoate(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methy}-3- (phenylthio)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R) -1-(hydroxymethyl)-2-methylpropyl]amino}methyl) propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R,2S)-1-(hydroxymethyl)-2-methylbutyl]amino}methyl) propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(phenoxymethyl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(2,4-difluorophenyl)amino]-5-oxopentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(4,6-dimethylpyrimidin-2-yl)amino]-5-oxopentanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(3-methoxybenzoyl)-5- methylbenzoate(1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-dichiorophenyl)-4- oxobutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[4-(methoxycarbonyl)phenyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(4-acetylphenyl)amino]-5-oxopentanoate (1R,2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- (phenylthio)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-({2-[(methylamino)carbonyl]phenyl}thio)propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-[(1-propylbutyl)thio]propanoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(4-ethoxyphenyl)amino]-4-oxobutanoate (1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[2-({[(3-methoxyphenyl)amino]carbonyl}oxy)ethyl]amino}methyl)propyl3-[(dipropylamino)carbonyl}-5-methylbenzoateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2,3-dihydro-1-benzofuran-5-yl)-N-(3-ethylbenzyl)-1,3-thiazole-4-carboxamideN-{(2R,3S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N-(3-methoxybenzyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-pentylmalonamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3- (trifluoromethoxy)benzamideN-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3- methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanamideN′-[4-(acetylamino)phenyl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)succinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(1-cyanoethyl)-N-(3-ethylbenzyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(5-phenyl-1,3,4-thiadiazol-2-yl)succinamide N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[2-(2-oxo-2-pyrrolidin-1-ylethoxy)phenyl]-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1,1-dioxidotetrahydro-2-thienyl)-N-(3-ethylbenzyl)acetamideN-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hex-1-yn-1-ylnicotinamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methoxyisoxazole-5- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dimethyl-1H-indole-7- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3-chlorophenyl)-N-(3-ethylbenzyl)-2-hydroxy-4-oxobutanamideN¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methoxyphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(1-methyl-1H-indol-3-yl)-2-oxoacetamide N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN¹-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzefle-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[5-(4-methyiphenyl)-2H-tetrazol-2-yl]acetamide N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-3-phenylisoxazole-4-carboxamide N-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N+,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-[(methylsulfonyl)acetyl]-N²-pentylglycinamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1H-indol-3-yl)-4- oxobut anamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(5-benzyl-1,3,4-thiadiazol-2-yl)-N-(3-ethylbenzyl)succinamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(3-fluoro-4-methoxypheriyl)-4-oxobutanamide ethyl4-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)piperidine-1-carboxylateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-fluorobenzoyl)-1H-pyrrole-2-carboxamideN¹-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(4-morpholin-4- ylphenyl)acetamideN-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluorornethoxy)phenyl]butyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-benzyl-N′-(1-cyclopropylethyl)-N-(3-ethylbenzyl)succinamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2,5-dimethylbenzoyl)-N-(3-methoxybenzyl)-5-methylbenzamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N -(2-methoxy-5-methyiphenyl]succinamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(3-hydroxyphenyl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-[hydroxy(2-methylphenyl)methyl]-N-(3-methoxybenzyl)-5-methylbenzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-(ethyithio)nicotinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-[4-(2-furoyl)piperazin-1-yl]-4-oxobutanamide N-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-oxoisoindoline-l- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(ethylthio)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)thieno [2,3-b]quinoline-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(4-methyl-1,3-oxazol-2- yl)benzamidehydrochloride N¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-(2-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}phenyl)-N-methyl- 2-furamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-(3-methoxyphenyl)-4-oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-cycloheptyl-5-methyl-N′,N′- dipropylisophthalamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3-fluoro-5-hydroxyphenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hydroxy-1H-indole-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,2-dimethylchromane-8- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-benzyl-N-(3-ethylbenzyl)pyrazine-2- carboxamide 4-oxide2-({[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-methoxybenzyl)amino]carbonyl}amino)-N,N-dipropylethanesulfonamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-benzyl-3- [(dipropylamino)sulfonyl]propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(4-methoxyphenyl)-4- oxobutanamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methyl-4-oxo-3,4-dihydrophthalazine-1-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3,4-dihydro-2H-1,5-benzodioxepine-7-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[4-(2,5-dioxopyrrolidin-1-yl)phenoxy]-N-(3-ethyllbenzyl)acetamideN¹-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamideN¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3-chloro-5-fluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′- dipropylpentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-6-fluoro-2-hydroxyquinoline-4-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-oxo-4-(2- thienyl)butanamideN³-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-methoxybenzyl)amino]carbonyl}-N¹,N¹-dipropyl-β-alaninamide N¹-[(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-1-(hydroxymethyl)-2-methyipropyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R,2S)-1-(hydroxymethyl)-2-methylbutyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(phenoxymethyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(2,4-difluorophenyl)-N-(3- ethylbenzyl)pentariediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(4,6-dimethylpyrimidin-2-yl)-N-(3-ethylbenzyl)pentanediamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(3-methoxybenzoyl)-N-(3-methoxybenzyl)-5-methylbenzamide N¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dichlorophenyl)-N-(3-ethylbenzyl)-4- oxobutanamidemethyl 4-{(2S,3R)-2-amino-4-[{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}(3-methoxybenzyl)amino]-3-hydroxybutyl}benzoateN′-(4-acetylphenyl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3- ethylbenzyl)pentanediamideN-{(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutyl}-N-(3-methoxybenzyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamide2-({3-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-3-oxopropyl}thio)-N- methylbenzamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-3-[(1-propylbutyl)thio]propanamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(4-ethoxyphenyl)-N-(3- ethylbenzyl)succinamideN¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide 2-([(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)(3-[(dipropylamino)carbonyl]-5- methylbenzoyl}amino) ethyl(3-methoxyphenyl)carbamate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino)methyl}propyl 3-(benzyloxy)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-2-hydroxy-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(pentafluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-hydroxyphenyl)-4- oxobutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 3-(piperidin-3- ylsulfonyl)benzoatedihydrochioride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-chloro-4-hydroxyquinoline-2-carboxylate (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(2-thienyl)propyl 5-(dipropylamino)-5-oxopentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-4- methylpentyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (6-oxo-3-phenylpyridazin-1(6H)-yl)acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{4-[(methylsulfonyl)amino]phenyl}propanoate(1R,2S)-2-amino-3-(4-fluoro-3-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4- methylphenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl 3-(2-chlorophenoxy) propanoate(1R,2S)-2-amino-3-(4-fluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4-chlorobenzoyl)-D- alaninate(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(4-methylphenyl)-4- oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[3-(trifluoromethyl)phenyl]amino}butanoate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenylyl{[(3-ethylbenzyl)amino]methyl}propyl (5-pyridin-2-yl-2H-tetrazol-2-yl)acetate (1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(3-methylphenyl)propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl isoxazole-5-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3,5- dimethoxyphenoxy)acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-hydroxybenzoate (1R,2S)-2-amino-3-(3-bromophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5- oxopentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino[methyl}propyl 4-{[5-(cyclopentylmethyl)-1,3,4-thiadiazol-2-yl]amino}-4-oxobutanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3-oxo-1,2-benzisothiazol-2(3H)-yl)acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-methyl-5-(pyrrolidin-1-ylcarbonyl)-1H-pyrrol-3-yl]amino}methyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-4- oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-naphthyl)-4- oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4,6-diethoxypyridine-2- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(5-methyl-1H-pyrrol-2-yl)-4-oxobutanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-({[2-(methylamino)ethyl]amino}sulfonyl)benzoate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-methyl-5-(4- methylbenzoyl)benzoate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1- [(benzylamino)methyl]propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(piperazin-1- ylsulfonyl)benzoatehydrochloride (1R,2S)-2-amino-1-[({2-[4-(aminosulfonyl)phenyl]ethyl}amino)methyl]-3-(3,5- difluorophenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-({[2-hydroxy-1-(hydroxymethyl)ethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(4-fluoro-3-methylphenyl)-1-{[(3-methyibutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[3-ethyibenzyl)amino]methyl}propyl 3-(3-oxo-2,1-benzisothiazol-1(3H)-yl)propanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2,6-dihydroxypyrimidin-4- yl)acetate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 5-(dipropylamino)-5- oxopentanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4- hydroxyphenyl)propyl3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-2-methyl-4-oxobutanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-5-[(2-pyridin-2-ylethyl)amino]pentanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(anilinocarbonyl)glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6- dimethoxybenzoyl)glycinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1,3-dithian-2-yl)-3- furoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-[2-oxo-2- (propylamino)ethyl]benzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3- bromophenyl)propyl3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-iodobenzyl)amino]methyl}propyl 3-(2-fluorophenyl)propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-methylthiophene-2- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [4-(benzyloxy)phenyl]acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(5,7-dimethyl[1,2,4]triazolo[4,3-a]pyrimidin-3-yl)thio]acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(1-acetyl-2,3-dihydro-1H-indol-7-yl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-[(3-acetylphenyl)amino]-5-oxopentanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4-chlorophenoxy)-2- hydroxypropanoateN³-[(1S,2R)-3-(benzylamino)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxypropyl]-N¹,N¹-dipropylbenzene-1,3,5-tricarboxamide (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3-methylphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1H-indole-7-carboxylate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(3 methylphenyl)propyl 3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1,2,3-thiadiazol-4- yl) benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3(4-methylphenyl)propyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-fluoro-5-(trifluoromethyl)phenyl]propyl 3-[(dipropylamino) carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [1-methyl-3-(methylthio)-1H-indol-2-yl]acetate (1R,2S)-2-amino-3-(3,5 dichlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino) carbonyl]-5-methylbenzoate (1R,2s)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(2-{[4-(1,3-oxazol-5-yl)phenyl]amino}-2-oxoethyl)thio]acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2-furyl)-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)propanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [2-(acetylamino)-1,3-thiazol-4-yl]acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(4-methyl-4H-1,2,4-triazol-3-yl)thio](phenyl)acetate (1R,2S)-2-amino-3-(4-chlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(1,3-benzothiazol-2- yl) butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(3-chloro-4-fluorophenyl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl [(2-oxo-2,3-dihydroquinazolin-4-yl)thio]acetateN-≡(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(benzyloxy)-N-(3-ethylbenzyl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1S)-2-hydroxy-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-2-hydroxy-4-(peritafluorophenyl)butyl]-5-methyl-N′,N′-dipropyl-N-[3-(trifluoromethyl)benzyl]isophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(4-hydroxyphenyl)-4- oxobutanamideN-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl)-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(piperidin-3- ylsulfonyl)benzamidedihydrochioride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethylbenzyl)-4-hydroxyquinoline-2-carboxamide N-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamideN-[(2R,3S)-3-amino-2-hydroxy-5-methylhexyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(6-oxo-3-phenylpyridazin-1(6H)-yl)acetamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-{4-](methylsulfonyl)amino]phenyl}propanamideN¹-[(2R,3S)-3-amino-4-(4-fluoro-3-methylphenyl)-2-hydroxybutyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-chlorophenoxy)-N-(3- iodobenzyl)propanamideN¹-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(4-methylphenyl)-4- oxobutanamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-oxo-4-{[3-(trifluoromethyl)phenyl]amino}butanoateN-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-5-methyl-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)isoxazole-5-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(3,5-dimethoxyphenoxy)-N-(3- ethylbenzyl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(3-ethylberizyl)-3-hydroxybenzamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-[5-(cyclopentylmethyl)-1,3,4-thiadiazol-2-yl]-N-(3-ethylbenzyl)succinamide N¹-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-methyl-N-[1-methyl-5-(pyrrolidin-1-ylcarbonyl)-1H-pyrrol-3-yl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethylbenzyl)-4- oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-naphthyl)-4- oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4,6-diethoxy-N-(3-ethylbenzyl)pyridine-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(5-methyl-1H-pyrrol-2-yl) -4-oxobutanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutzyl]-N-(3-ethylbenzyl)-3-({[2-(methylamino)ethyl]amino}sulfonyl)benzamide hydrochlorideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-3-methyl-5-(4- methybenzoyl)benzamideN-[(2R,3S)-3-amino-4-(1,3-benzodioxxl-5-yl)-2hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophrnyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(piperazin-1- ylsulfonyl)benzamidehydrochloride N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-{2-[4- aminosulfonyl)phenyl]ethyl}-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]-5-methyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-4-(4-fluoro-3-methylphenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(3-oxo-2,1-benzisothiazol-1(3H)-yl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2,6-dihydroxypyrimidin-4-yl)-N-(3-ethylbenzyl)acetamide N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-N-benzyl-3-[(dipropylamino)sulfonyl]propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethylbenzyl)-2-methyl-4-oxobutanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(2-pyridin-2- ylethyl)pentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(anilinocarbonyl)-N¹-(3- ethylbenzyl)glycinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1,3-dithian-2-yl)-N-(3-ethylbenzyl)-3- furamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[2-oxo-2- (propylamino)ethyl]benzamideN-[(2R,3S)-3-amino-4-(3-bromophenyl)-2-hydroxybutyl]-N-benzyl-3-[(dipropylamino)sulfonyl]propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-fluorophenyl)-N-(3-iodobenzyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-methylthiophene-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[4-(benzyloxy)phenyl]-N-(3- iodobenzyl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-[(5,7-dimethyl[1,2,4]triazolo[4,3-a]pyrimidin-3-yl)thio]-N-(3-ethylbenzyl)acetamideN′-(1-acetyl-2,3-dihydro-1H-indol-7-yl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybuty]-N-(3-ethylbenzyl)succinamide N′-(3-acetyiphenyl)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3- ethylbenzyl)pentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4-chlorophenoxy)-N-(3-ethylbenzyl)-2-hydroxypropanamide N³-[(1S,2R)-3-(benzylamino)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxypropyl]-N¹,N¹-dipropylbenzene-1,3,5-tricarboxamide N¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1H-indole-7-carboxamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(1,2,3-thiadiazol-4- yl)benzamideN-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamideN-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[1-methyl-3-(methylthio)-1H-indol-2-yl]acetamide N-[(2R,3S)-3-amino-4-(3,5-dichlorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N∝,N′- dipropylisophthalamide2-({2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-2-oxoethyl}thio)-N-[4-(1,3-oxazol-5-yl)phenyl]acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-(2-furyl)-4-oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)propanamide2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3- ethylbenzyl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-3-ethylbenzyl)-2-[(4-methyl-4H-1,2,4-triazol-3-yl)thio]-2-2phenylacetamideN-[(2R,3S)-3-amino-4-(4-chlorophenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbuty)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(1,3-benzothiazol-2-yl)-N-(3- ethylbenzyl)butanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3-chloro-4-fluorophenyl)-N-(3- ethylbenzyl)succinamideN-{(2R,3S)-3-amino-4-(3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-5-methyl-N-(3-methylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(2-oxo-2,3-dihydroquinazolin-4-yl)thio]acetamide(1R,2S)-2-amino-3-(3,5-dufluorophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-methyl-5-(2- methylbenzoate(1R,2S)-2-amino-3-(4-hydroxophenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5- oxopentanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(4- methylphenyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-([(3-ethylbenzyl)amino)methyl]propyl 4-propoxybenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1-methyl-1H-indole-2- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-difluorophenyl)-2-methoxy-4-oxobutanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [3-(2-thienyl)-1H-pyrazol-1- yl]acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl S-anilino-5-oxopentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2-thioxo-1,3-benzothiazol-3(2H)-yl)acetate (1R,2S)-2-amino-1-[(benzylamino)methyl]-3-cyclohexyipropyl 3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-(4-methoxyphenyl)propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3-hydroxy-4- methylphenyl)acetate(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 7-fluoro-4H-imidazo[5,1-C][1,4]benzoxazine-3-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 1-benzofuran-3-carboxylate(1R,2S)-2-amino-3-(3,s-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(3,4-dichiorophenyl)amino]-3-oxopropanoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-fluoro-5-(trifluoromethyl)phenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-hydroxy-1-methylethyl]amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3- methylphenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-5-(pyridin-3- ylamino)pentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-methyl-4-oxo-4H-chromene-6-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl ({2-[(5-methylisoxazol-3-yl)amino]-2-oxoethyl}thio)acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(1H-imidazol-1-yl)propyl[amino}methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(4-hydroxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-(2-thienyl)propyl 3-[(dipropylamino)suflonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(2,2-dimethyipropanoyl)amino]-2-hydroxybenzoate(1R,2S)-2-amino-3-(3-methoxyphenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(4-fluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-{[(3-methoxybenzyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethyl)phenyl]propyl 3-[(dipropylamino)carbonyl]-5-methyibenzoate (1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-(2-furoylamino)hexanoate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(1-phenyl-4,5-dihydro-1H-tetrazol-5-yl)thio]acetate (1S,2S)-2-amino-3-phenyl-1-({[3-(trifiuoromethyl)benzyl]amino}methyl)propyl 3-{[(3-methoxybenzyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl 4-(3,4-dihydro-2H-chromen-6-yl)-4-oxobutanoate (1R,2S)-2-amino-3-(3-methoxyphenyl)-1-{[(3-methylbutyl)amino[methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3-fluoro-4-methylphenyl)-1-{[(3-methoxybenzyl)amino]methyl}propyl 5-(dipropylamino)-5- oxopentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl indolizine-2-carboxylate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(trifluoromethoxy)phenyl]propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl nicotinate 1-oxide(1R,2S)-2-amino-3-[3-(benzyloxy)-5-fluorophenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-iodobenzyl)amino]methyl}propyl [(aminocarbonyl)oxy]acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2,3-dihydro-1H-cyclopenta[b]quinoline-9-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-methyl-1H-pyrazole-5- carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-(benzoylamino)pentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4- [(methoxymethyl)thio]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1,3-benzothiazol-2-yl)-3-methoxypropanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-{[(methylamino)carbonyl]amino}-3-(3-thienyl)propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-pyridin-2-ylthiopherle-2- carboxylate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-[3-(benzyloxy)-5-fluorophenyl]propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (5,6-dimethyl-2,4-dipxo-1,2,3,4-tetrahydropyridin-3-yl)acetate(1R,2S)-2-amino-3-(3-fluoro-4-methoxyphenyl)-1-{[(3-methylbutyl)amino]methyl)propyl 3-[(dipropylamino)carbonyl]-5-methylbenzoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl)propyl 2-isobutyl-1,3-dioxoisoindoline-5-carboxylate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[3-ethylbenzyl)amino]methyl}propyl 5-(acetylamino)-2-furoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(4- methylphenyl)acetyl]glycinate(1R,2s)-2-amino-3-(3,5-difluorophenyl-1-{[(3-methylbutyl)amino]methyl}propyl isoquinoline-4-carboxylate(1R,2S)-2-amino-3-[3-(benzyloxy)phenyl]-1-{[(3-methylbutyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (4-hydroxy-3- methoxyphenyl)acetate(lR,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(4-phenyl-4H-1,2,4-triazol-3-yl)thio]acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (3,5-dimethoxyphenyl)acetate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(3- methoxyphenyl)propyl3-[(dipropylamino)carbonyl]-5- methylbenzoate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl (2-ethyl-4H-[1,2,4]triazolo[1,5-a]benzimidazol-4-yl)acetate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2- furyl)propyl3-[(dipropylamino)carbonyl]-5-methylbenzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 7-chloro-1-benzofuran-2- carboxylate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-oxo-2H-1,3-benzoxazin-3(4H)-yl)propanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl(pyrimidin-2-ylthio)acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-{[3-(aminocarbonyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]amino}-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl quinoline-6-carboxylate(1R,2S)-2-amino-1-[(benzylamino)methyl]-3-(2- furyl)propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(1H-indol-3-yl)-1H-pyrazole-5-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4-{[(methylamino)carbonothioyl]amino}benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 6-chloronicotinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3-hydroxyphenyl)-4- oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (phthalazin-1-ylthio)acetate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl [(1-oxidopyridin-2- yl)thio]acetate(1R,2S)-2-amino-3-(3,5-difluoropheny1)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(acetylamino)-5-fluoro-1H-indole-2-carboxylate (1S,2S)-2-amino-3-phenyl-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-{[(3-chlorobenzyl)amino]sulfonyl}benzoate(1R,2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-{[(3-methoxybenzyl)amino]methyl}propyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1- [(benzylamino)methyl]propyl3-(aminocarbonyl)-5- [(dipropylamino)carbonyl]benzoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-(3,4-dichlorophenyl)-2-hydroxy-3-methyl-4-oxobutanoate(1R,2S)-2-amino-1-{[(3-methylbutyl)amino]methyl}-3-[3-(trifluoromethoxy)phenyl]propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(5-methyl-1,3,4-thiadiazol-2-yl)amino]-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2-ethyl-1H-benzimidazol-1- yl)acetate(1R,2S)-2-amino-3-(1,3-benzodioxol-5-yl)-1-{[(3-methoxybenzyl)amino)methyl)propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[3-ethylbenzyl)amino)methyl}propyl 3-(2-oxo-1,3-benzoxazol-3(2H)-yl)propanoate (1R,2S)-2-amino-3-(3,5-dichlorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3- [(dipropylamino)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-[(6-methylpyridin-2-yl)amino]-4-oxobutanoate4-((1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl) 3-ethyl (4R)-1,3-oxazolidine-3,4-dicarboxylateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-3-methyl-5-(2- methylbenzoyl)benzamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl)-N-(3-methoxybenzyl)-N′,N′-dipropylpentanediamideN₁-[(2R,3S)-3-amino-2-hydroxy-4-(4-methylphenyl)butyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-propoxybenzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1-methyl-1H-indole-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-5-chloro-N-(3-ethylbenzyl)-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-difluorophenyl)-N-(3-ethylbenzyl)-2-methoxy-4-oxobutanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[3-(2-thienyl)-1H-pyrazol-l-yl]acetamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-phenylpentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(2-thioxo-1,3-benzothiazol-3(2H)-yl)acetamideN-[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butyl]-N¹-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxarnideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(3-hydroxy-4- methyiphenyl)acetamideN-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-7-fluoro-4H-imidazo[5,1-C][1,4]benzoxazine-3-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-N-(3-ethylbenzyl)-4-oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-1-benzofuran-3-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N′-(3,4-dichiorophenyl)-N-(3- ethylbenzyl)malonamideN¹-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl)-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[(1R)-2-hydroxy-1-methylethyl]-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(3-methylphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-pyridin-3- ylpentanediamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-methyl-4-oxo-4H-chromene 6-carboxylate2-({2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-2-oxoethyl}thio)-N-(5-methylisoxazol-3-yl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-[3-(1H-imidazol-1-yl)propyl]-5-methyl-N′,N′-dipropylisophthalamide N-{(2R,3S)-3-amino-4-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamideN-[(2R,3S)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-2-hydroxy-4-(2-thienyl)butyl]-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-[(2,2-dimethyipropanoyl)amino]-N-(3-ethylbenzyl)-2-hydroxybenzamide N-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-5-methyl-N-(3-methylbutyl)-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(4-fluorophenyl)-2-hydroxybutyl]-3-{[(3-methoxybenzyl)amino]sulfonyl}-N-[3-(trifluoromethyl)benzyl]benzamide N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethyl)phenyl]butya}smethypN (3-methylbutyl)N′,N′-dipropylisophthalamideN-{6-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-6-oxohexyl}1-2-furamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyly2.hydroxybutyl]-N-(3-ethylbenzyl)-2 [(1-phenyl-4,5-dihydro-1H-tetrazol-5-yl)thio]acetamide N-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(3- methoxybenzyl)aminosuflonyl)-N-]-[3- (trifluoromethyl) benzyl]benzamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dihydro-2H-chromen-6-yl)-N-(3- ethylbenzyl)-4-oxobutanamide N¹-[(2R,3S)-3-amino-2-hydroxy-4- 3-methoxyphenyl)butyl]-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3-fluoro-4-methylphenyl)-2-hydroxybutyl]-N-(3-methoxybenzyl)-N′,N′- dipropylpentanediamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)indolizine-2-carboxamideN-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-N-benzyl-5-methyl-N′,N′-dipropylisophthalamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)nicotinamide 1-oxideN-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-3-[(dipropylamino)sulfonyl]-N-(3- methylbutyl)propanamide2-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-iodobenzyl)amino]-2-oxoethyl carbamateN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2,3-dihydro-1H-cyclopenta[b]quinoline-9-carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-methyl-1H-pyrazole-5- carboxamideN-{5-[[(2R,3S)-3-amino-4-(3S-dif1uorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-5-oxopentyl}benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4- [(methoxymethyl)thio]benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(1,3-benzothiazol-2-yl)-N-(3-ethylbenzyl)-3-methoxypropanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(methylamino)carbonyl]amino}-3-(3-thieriyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-pyridin-2-ylthiophene-2- carboxamideN¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)-5-fluorophenyl]-2-hydroxybutyl}-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3-fluoro-4-methoxyphenyl)-2-hydroxybutyl]-5-methyl-N-(3-methylbutyl)-N′,N′- dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-isobutyl-1,3-dioxoisoindolme-5-carboxamide 5-(acetylamino)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-furamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-[(4-methoxyphenyl)acetyl]glycinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)isoquinoline-4-carboxamideN¹-{(2R,3S)-3-amino-4-[3-(benzyloxy)phenyl]-2-hydroxybutyl}-N¹-(3-methylbutyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(4-hydroxy-3- methoxyphenyl)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(4-phenyl-4H-1,2,4-triazol-3-yl)thio]acetamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(3,5-dimethoxyphenyl)-N-(3- ethylbenzyl)acetamideN-[(2R,3S)-3-amino-2-hydroxy-4-(3-methoxyphenyl)butyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(2-ethyl-4H-[1,2,4]triazolo[1,5-a]benzimidazol-4-yl) acetamideN-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N-benzyl-5-methyl-N′,N′-dipropylisophthalamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-7-chloro-N-(3-ethylbenzyl)-1-benzofuran-2- carboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(3-ethylbenzyl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-oxo-2H-1,3-benzoxazin-3(4H)-yl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(pyrimidin-2- ylthio)acetamideN′-[3-(aminocarbonyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl) succinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)quinoline-6-carboxamideN¹-[(2R,3S)-3-amino-4-(2-furyl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropylbenzene-1,3,5-tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-N-(3-ethylbenzyl)-4-oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(1H-indol-3-yl)-1H-pyrazole-5-carboxamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4-{[(methylamino)carbonothicyl]amino}benzamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-6-chloro-N-(3-ethylbenzyl)nicotinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl[-N-(3-ethylbenzyl)-4-(3-hydroxyphenyl)-4- oxobutanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-(phthalazin-1- ylthio)acetamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-[(1-oxidopyridin-2- yl)thio]acetamide3-(acetylamino)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-fluoro-1H-indole-2-carboxamideN-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(3-chlorobenzyl)amino]sulfonyl}-N-[3- (trifluoromethyl)benzyl]benzamideN¹-{(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-2-hydroxybutyl}-N′-(3-methoxybenzyl)-N³,N³-dipropylbenzene-1,3,5-tricarboxamide N¹-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-N¹-benzyl-N³,N³-dipropy1benzene1,3,5- tricarboxamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(3,4-dichiorophenyl)-N-(3-ethylbenzyl)-2-hydroxy-3-methyl-4-oxobutanamide N-{(2R,3S)-3-amino-2-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl}-3-[(dipropylamino)sulfonyl]-N-(3-methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(5-methyl-1,3,4-thiadiazol-2-yl)succinamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-2-(2-ethyl-1H-benzimidazol-1-yl)-N-(3-ethylbenzyl)acetamide N-[(2R,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3-methoxybenzyl)propanamide N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-3-(2-oxo-1,3-benzoxazol-3(2H)-yl)propanamide N-[(2R,3S)-3-amino-4-(3,5-dichiorophenyl)-2-hydroxybutyl]-3-[(dipropylamino)sulfonyl]-N-(3- methylbutyl)propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-N′-(6-methylpyridin-2- yl)succinamideethyl(4R)-4-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-1,3-oxazolidine-3-carboxylate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfinyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3ethylbenzyl)amino]methyl}propyl S-butyl-N-(methoxycarbonyl)-D-cysteinate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(4,4,4-trifluorobutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(4,4,4-trifluorobutyl)sulfinyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-S-(4,4,4-trifluorobutyl)-D-cysteinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propya 3-(butylsulfonyl)-N-[(2,2,2-trifluoroethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(2-cyanoethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-{[(3R)-pyrrolidin-3-yloxy]carbonyl}-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[2-(acetylamino)ethoxy]carbonyl}-3-(butylsulfonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(pyridin-3-ylmethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(pyridin-4-ylmethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)- D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5difluorophenyl)propyl 3-(butylsulfonyl)-N-[(2-cyanoethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-D-aianinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl N-[(2-cyanoethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl N- {[2-(acetylamino)ethoxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-(methoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[2-(diethylamino)-2-oxoethoxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(methoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(isopropoxycarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(cyclopropylmethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]- D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(allyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-cyanoethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-aifluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[2-(acetylamino)ethoxy]carbonyl}-3-[(1-propylbutyl)sultonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-3-ylmethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-4-ylmethoxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-[(benzyloxy)carbonyl]amino}-4-(methylsulfonyl)butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-(butylsulfonyl)-L-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1R)-2-methoxy-1-phenylethyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[(1S)-2-methoxy-1-phenylethyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethyiphenyl)cyclopropyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(prop-2-yn-1-yloxy)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-methoxyethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1-acetylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(lR,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}-L-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sultonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sultonyl]-L-alaninate(1R,2S)1-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethyiphenyl)cyclopropyl]amino}methyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-[(cyclopropyiamino)methyl]-3-(3,5-difluorophenyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(cyclopropylmethyl)amino]methyl}-3-(3,5-ditiuorophenyl)propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylphenyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]aianinate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-[({2-[3-(trifluoromethyl)phenyl]ethyl}amino)methyl]propyl N-[(benzyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(pyridin-3-ylmethoxy)carbonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3S)-tetrahydrofuran-3-yloxy]carbonyl}alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-tetrahydrofuran-3-yloxy]carbonyl}alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl3-[(1-propylbutyl)sulfonyl]-N- {[(3S)-tetrahydrofuran-3-yloxy]carbonyl}alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1-acetylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-pyrrolidin-3-yloxy]carbonyl}alaninate(1R,2S)-2-amino-3-(3,5-difluoropheny)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1-benzylpyrrolidin-3-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(3R)-1,1-dioxidotetrahydro-3-thienyl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[(3R)-tetrahydro-3-thienyloxy]carbonyl}alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N- [(cyclopentyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenylyl{[(3-ethylbenzyl)amino]methyl}propyl N-[(cyclohexyloxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl 3-[(1-propylbutyl)sulfonyl]-N-(tetrahydro-2H-pyran-4-yloxy)carbonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({(1-(methylsulfonyl)piperidin-4-yl]oxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({(1-acetylpiperidin-4-yl)oxy]carbonyl}-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(2R)-5-oxopyrrolidin-2-yl]methoxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-({[(2S)-5-oxopyrrolidin-2-yl]methoxy}carbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2-methoxyethoxy)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluoropheflyl)-1-([(3-ethylbenzyl)amino]methyl}propyl N-[(benzyloxy)carbonyl]-3-(butylsulfonyl)alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(benzyloxy)carbonyl]-3-[(1- propylbutyl)sulfonyl]alaninateN-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-hydroxy-4- (phenylsulfonyl)butanamidehydrochloride (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N2-[(benzyloxy)carbonyl]-N⁵,N⁵-dipropyl-L-glutaminate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N²-[(benzyloxy)carbonyl]-N⁵,N⁵-dipropyl-D-glutaminate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(3,3,3-trifluoropropanoyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(trifluoroacetyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-3-(butylsulfonyl)- D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-isonicotinoyl-D-alaninate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(cyclopropylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl β-alanyl-3-(butylsulfonyl)- D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl glycyl-3-(butylsulfonyl)-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N,N-dimethylglycyl-3-(butylsulfonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N,N-dimethyl-β-alanyl-3-(butylsulfonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxyacetyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(pyridin-3-ylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-{[3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(1H-imidazol-4-ylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-hydroxy-2-[(methoxycarbonyl)amino]nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(6-hydroxypyridin-3-yl)carbonyl]-D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl 3-(butylsulfonyl)-N-(pyridin-3-ylcarbonyl)-D-alaninate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-acetyl-3-(butylsulfonyl)- D-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl N-(cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl N-acetyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-bromopyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-chloropyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-fluorobenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(5-methylpyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-phenylglycyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-{[3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(1,3-thiazol-4-ylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(1-acetylpiperidin-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[4-(acetylamino)butanoyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-□-alanyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(chloroacetyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(methoxyacetyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-methoxypropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,2-dimethylpropanoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-isobutyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-butyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-acetyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-[(1-propylbutyl)sulfonyl]-N-(pyridin-3-ylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethyiphenyl)cyclopropyl]amino}methyl)propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethyiphenyl)cyclopropyl]amino}methyl)propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylphenyl)cyclopropyl)amino]methyl}propy) 3-[1-propylbutyl)sunfonyl]-N-(pyridin-3-ylcarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-propionyl-3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(pyridin-3-ylcarbonyl)alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl N-isonicotinoyl-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)carbonyl]-3-[(1- propylbutyl)sulfonyl]alaninate(lR,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-D-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 5-oxo-D-prolyl-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[3-(4-oxo-2-thaoxo-1,3-thiazolidin-3-yl)propanoyl]-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(piperidin-4-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(2,4-dimethyl-1,3-thiazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]carbonyl}-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(3,5-dimethylisoxazol-4-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(1H-pyrazol-4-ylcarbonyl)alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-imidazol-5-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-imidazol-4-ylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(pyrazin-2-ylcarbonyl)alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2,6-dihydroxyisonicotinoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl)propyl N-[(6-hydroxypyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sultonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl N-[(6-chloropyridin-3-yl)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl N-isonicotinoyi-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(pyridin-3-ylcarbonyl)alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(pyridin-2-ylcarbonyl)alaninate(1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(1H-indol-6-ylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate hydrochloride(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethyibenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-(3,4,5-trimethoxybenzoyl)alaninate(1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(2-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{](3-ethylbenzyl)amino]methyl}propyl N-(3-hydroxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditiuorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-methylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-ethylbenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-chlorobenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[4-(trifluoromethyl)benzoyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(4-methoxybenzoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[4-(trifluoromethyl)benzoyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(cyclohexylcarbonyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-benzoyl-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl N-benzoyl-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(benzoylamino)-2-{[(1-propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-(cyclopropylacetyl)-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(methylsulfonyl)acetyl]-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(methylthio)acetyl]-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropylN-[4-(methylamino)-4-oxobutanoyl]-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-(methylsulfonyl)glycyl-3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-acetyl-3-(phenylsulfonyl)alaninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2-[(4-methoxy-4-oxobutanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-{[(benzyloxy)carbonyl]amino}-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(3-ethoxy-3-oxopropanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN²-(4-methoxy-4-oxobutanoyl)-N⁵,N⁵-dipropyl-D- glutaminate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(4-methoxy-4-oxobutanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenyipropyl(2R)-2-[(5-methoxy-5-oxopentanoyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-(acetyloxy)-3-(butylsulfonyl)propanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl S-butyl-D-cysteinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfinyl)-D- alaninate(lR,2S)-2-amino-3-(3,5-difluorophenylb)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-L alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-(butylsulfonyl)-D alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-[(1-propylbutyl)sulfonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]- L-alaninate(1R,2S)-2-amino-1-[(cyclopropylamino)methyl]-3-(3,5-difluorophenyl)propyl 3-[(1-propylbutyl)sulfonyl]-D alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-methylbutyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]- D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]- D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyllpropyl 3-[(1- propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenoxyacetyl)-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-{[(5-chloro-2-thienyl)thio]peroxy}-3-[(1-propylbutyl)sulfonyl]alaninate(1R,2S)-2-amino-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl N-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninate (1R,2S)-3-(3,5-ditluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}-2-(methylamino)propyl N-[(benzylamino)carbonyl]-3-[(1-propylbutyl)sulfonyl]alaninate4-{[(1R,2S)-3-(3,5-difluorophenyl)-1-{](3-ethylbenzyl)amino]methyl}-2-(methylamino)propyl]oxy}-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoic acid4-[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]-3-{[(3-methylbutyl) sultonyl]methyl}-4- oxobutanoicacid 1-((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl) 4-methyl methylbutyl)sulfonyl]methyl}succinate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl4-amino-2-{[(3-methylbutyl)sulfonyl]methyl}-4- oxobutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl4-(methylamino)-2-{[(3- methylbutyl)sulfonyl]methyl}-4-oxobutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl4-(dimethylamino)-2-{[(3- methylbutyl)sulfonyl]methyl}-4-oxobutanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-l-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoate(1R,2R)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-(ethylsulfonyl)-2- {[(isobutylsulfonyl)amino]methyl}propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-(ethylthio)-2- {[(isobutylsulfonyl)amino]methyl}propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl(2S)-2-{[(3-methylbutyl)sulfonyl]amino}-4- (methylsulfonyl)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(3-methylbutyl)sulfonyl]-L-methioninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl3-(acetylthio)-2-{[(3- methylbutyl)sulfonyl]methyl}propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-hydroxy-3-[(1-propylbutyl)sulfonyl]propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl)-3- phenylpropyl2-hydroxy-3-[(3-methylbutyl)sulfonyl]propanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-hydroxy-3-[(3- methoxyphenyl)sulfonyl]propanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 2-hydroxy-4- (phenylsulfonyl)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-hydroxy-4-[(3-methylbutyl)sulfonyl]butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl4-[(3-methylbutyl)sulfonyl]-2-phenoxybutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl2-(3-methoxyphenoxy)-4-[(3- methylbutyl)sulfonyl]butanoate3-{1-{[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]carbonyl}-3-[(3-methyibutyl)sulfonyl]propoxy}benzoic acid methyl3-{[-{[((1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl)oxy]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-hydroxy-4-(phenylsultonyl)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-hydroxy-4-(phenylthio)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-methoxy-4-(phenylsulfonyl)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-methoxy-4-(phenylthio)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl4-(phenylsultonyl)-2-propoxybutanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl2-(benzyloxy)-4-(phenylsultonyl)butanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropylN-[(benzyloxy)carbonyl]methioninate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl(2S)-2-amino-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2S)-2-[(2-methoxy-2-oxoethyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenylpropyl(2R)-2-amino-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(2-ethoxy-2-oxoethyl)amino]-5-oxo-5-piperidin-1-ylpentanoate(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3-phenylpropyl(2R)-2-[(4-ethoxy-4-oxobutyl)amino]-5-oxo-5-piperidin-1-ylpentanoate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-[(methoxycarbonyl)amino]-4-oxooctanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-butyl-N-(methoxycarbonyl)-D-homoserinate (1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxolan-2-yl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4,4-difluoro-2-[(methoxycarbonyl)amino]octanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-fluoro-2-[(methoxycarbonyl)amino]octanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-[(methoxycarbonyl)amino]-5-oxononanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-hydroxy-2-[(methoxycarbonyl)amino]nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxolan-2-yl)-2-[(methoxycarbonyl)amino]butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxan-2-yl)-2-[(methoxycarbonyl)amino]butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-fluoro-2-[(methoxycarbonyl)amino]nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5,5-difluoro-2-[(methoxycarbonyl)amino]nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,29)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl[propyl 3-(butylsulfonyl)-N-(methoxycarbonyl)-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-s-yl)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsultonyl)-N-[(3-methyl-1H-pyrazol-s-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl]propyl 3-(butylsulfonyl)-N-[(3-methyl-1H-pyrazol-5-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-{[(methylamino)carbonyl]amino}-4-oxooctanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 4-butyl-N[(methylamino)carbonyl]-D-homoserinate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxolan-2-yl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4,4-difluoro-2-{[(methylamino)carbonyl]amino}octanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-fluoro-2-{[(methylamino)carbonyl]amino}octanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-2-[methylamino)carbonyl]amino}-5-oxononanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylberizyl)amino]methyl}propyl (2R)-5-hydroxy-2-[(methylamino)carbonyl]amino}nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxolan-2-yl)-2-{[(methylamino)carbonyl]amino}butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-4-(2-butyl-1,3-dioxan-2-yl)-2-{](methylamino)carbonyl]amino}butanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5-fluoro-2-{[(methylamino)carbonyl]amino}nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl (2R)-5,5-difluoro-2-{[(methylamino)carbonyl]amino}nonanoate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynyiphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl]propyl 3-(butylsulfonyl)-N-[(methylamino)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethynylbenzyl)amino]methyl}propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D-alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[3-(trifluoromethyl)benzyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-({[1-(3-ethynylphenyl)cyclopropyl]amino}methyl)propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D- alaninate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-[({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)methyl]propyl 3-(butylsulfonyl)-N-[(4-methyl-1H-pyrazol-1-yl)carbonyl]-D- alaninatebenzyl[(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3- ethylbenzyl)amino]carbonyl}-3-(methylsulfonyl)propyl]carbamate(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-[(1-propylbutyl)sulfonyl]-N-[(tetrahydro-2H-pyran-4-yloxy)carbonyl]alaninateS-(3-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino[-2-{[(3-methylbutyl)sulfonyl]methyl}-3-oxopropyl)ethanethioateN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-(3-methoxyphenoxy)-4-[(3-methylbutyl)sulfonyl]butanamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-N²-(3,3,3-trifluoropropanoyl)-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-N²-(trifluoroacetyl)-D-alaninamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N-(3-methoxybenzyl)-4-(phenylthio)butanamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N²-(cyclopropylcarbonyl)-N¹-(3-ethylbenzyl)-D-alaninamideβ-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D- alaninamideglycyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D- alaninamide(1R,2S)-2-amino-1-{[(3-methoxybenzyl)amino]methyl}-3- phenyipropyl(2R)-2-[(4-ethoxy-4-oxobutyl)amino]-5-oxo-5- piperidin-1-ylpentanoateN,N-dimethyl-β-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D-alaninamide N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-N²-(methoxyacetyl)-D-alaninamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(2-butyl-1,3-dioxan-2-yl)-N-(methoxycarbonyl)-D-alaninateN²-acetyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-cyclopropyl-N²-(cyclopropylcarbonyl)-3-[(1-propylbutyl)sulfonyl]-D-aianinamideN²-acetyl-N¹-[(2R,3S)-3-amino-4-(3,5-difiucrophenyl)-2-hydroxybutyl]-N¹-(3-methyibutyl)-3-[(1-propylbutyl)sulfonyl]-D-aianinamideN-phenylglycyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN-acetyl-β-alanyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(chloroacetyl)-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-aianinamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(methoxyacetyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(3-methoxypropanoyl)-3-[(1-propylbutyl)sulfonyf]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-(2,2-dimethylpropanoyl)-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-isobutyryl-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN²-acetyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-ditluorophenyl)-2-hydroxybutyl[-N²-(cyclopropylcarbonyl)-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-propionyl-3-[(1-propylbutyl)sulfonyl]-D-alaninamide5-oxo-D-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sultonyl]alaninamide hydrochloride5-oxo-L-prolyl-N¹-[(2R,3S)-3-amino-4-(3,5-ditluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-[3-(4-oxo-2-thioxo-1,3-thiazolidin-3-yl)propanoyl]-3-[(1- propylbutyl) sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(1H-imidazoi-4-ylacetyl)-3-[(1-propylbutyl)sultonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(3-phenylpropanoyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN-(3-[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-3-oxo-2-{[(1-propylbutyl)sulfonyl]methyl}propyl)benzamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N²-(cyclopropylacetyl)-N¹-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylsulfonyl)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(methylthio)acetyl]-3-[(1-propylbutyl)sulfonyl]alaninamideN-(methylsulfonyl)glycyl-N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN²-acetyl-N¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-3-(phenylsulfonyl)alaninamide2-[[(2R,3S)-3-amino-4-(3,5-ditluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]-1- [(butylsulfonyl)methyl]-2-oxoethylacetate N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-S-butyl-N¹-(3-ethylbenzyl)-D-cysteinamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfinyl)-N¹-(3-ethylbenzyl)-D- alaninamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-D- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethylbenzyl)-L- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-methylbutyl)-D- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-[1-(3-ethylphenyl)cyclopropyl]-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-L-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-cyclopropyl-3-[(1-propylbutyl)sulfonyl]-D- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-methylbutyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-3-[(1- propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenoxyacetyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N²-{[(5-chloro-2-thienyl)thio]peroxy}-N¹-(3-ethylbenzyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N¹-(3-ethylbenzyl)-N²-(phenylsulfonyl)-3-[(1-propylbutyl)sulfonyl]alaninamideN²-[(benzylamino)carbonyl]-N¹-[(2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)butyl]-N¹-(3-ethylbenzyl)-3-[(1-propyibutyl)sulfonyl]alaninamide4-[[(2R,3S)-4-(3,5-difluorophenyl) -2-hydroxy-3-(methylamino)butyl](3-ethylbenzyl)amino]-4-oxo-3-{[(1-propylbutyl)sulfonyl]methyl}butanoic acid4-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-3-{[(3-methylbutyl)sulfonyl]methyl}-4- oxobutanoicacid methyl 4-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-3-{[(3-methylbutyl)sulfonyl]methyl}-4- oxobutanoateN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-2-{[(3- methylbutyl)sulfonyl]methyl}succinamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N⁴-methyl-2-{[(3- methylbutyl)sulfonyl]methyl}succinamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N⁴,N⁴-dimethyl-2-{[(3-methylbutyl)sulfonyl]methyl}succinamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N-(3-ethylbenzyl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanamide(1R,2S)-2-amino-3-(3,5-difluorophenyl)-1-{[(3-ethylbenzyl)amino]methyl}propyl 3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-{[(1- propylbutyl)sulfonyl]methyl}propanoateN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(ethylsulfonyl)-2-{[(isobutylsulfonyl)amino]methyl}-N-(3-methoxybenzyl)propanamide N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(ethylthio)-2-{[(isobutylsulfonyl)amino]methyl}-N-(3-methoxybenzyl)propanamide(2S)-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-{[(3-methylbutyl)sulfonyl]amino}-4-(methylsulfonyl)butanamideN¹-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N¹-(3-methoxybenzyl)-N²-[(3-methylbutyl)sulfonyl]-L-methioninamideS-(3-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]-2-{[(3-methylbutyl)sulfonyl]methyl}-3-oxopropyl)ethanethioateN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(1-propylbutyl)sulfonyl]propanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(3-methylbutyl)sultonyl]propariamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-3-[(3-methoxyphenyl)sulfonyl]propanamideN-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-hydroxy-4- (phenylsulfonyl)butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-[(3-methylbutyl)sulfonyl]butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-4-[(3-methylbutyl)sulfonyl]-2- phenoxybutanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-2-(3-methoxyphenoxy)-4-[(3-methylbutyl)sulfonyl]butanamide3-{1-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoic acid methyl3-{1-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl)amino]carbonyl}-3-[(3-methylbutyl)sulfonyl]propoxy}benzoateN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N-(3-methoxybenzyl)-4-(phenylthio)butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N-(3-methoxybenzyl)-4-(phenylthio)butanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-4-(phenylsulfonyl)-2-propoxybutanamideN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-(benzyloxy)-N-(3-methoxybenzyl)-4-(phenylsulfonyl)butanamide(2S)-2-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-5-oxo-5-piperidin-1- ylpentanamide(2R)-2-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(3-methoxybenzyl)-5-oxo-5-piperidin-1- ylpentanamidemethyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-oxoheptyl)carbamate methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3,3-difluoroheptyl)carbamate methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl)}-3-fluoroheptyl)carbamatemethyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-oxooctyl)carbamatemethyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-hydroxyoctyl)carbamatemethyl[(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-(2-butyl-1,3-dioxolan-2-yl)propyl]carbamate methyl [(1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-3-(2-butyl-1,3-dioxan-2- yl)propyl]carbamatemethyl ((1R)-1-{[[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4-fluorooctyl)carbamate methyl((1R)-1-{[[(2R,3S)-3-amino-4-(3,5- difluorophenyl)-2-hydroxybutyl](3-ethylbenzyl)amino]carbonyl}-4,4-difluorooctyl)carbamate(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-}[(methylamino)carbonyl]amino}-4-oxooctanamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-butyl-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-homoserinamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-butyl-1,3-dioxolan-2-yl)-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(2-butyl-1,3-dioxan-2-yl)-N¹-(3-ethylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4,4-difluoro-2-{[(methylamino)carbonyl]amino}octanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-4-fluoro-2-{[(methylamino)carbonyl]amino}octanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino}-5-oxononanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-hydroxy-2-{[(methylamino)carbonyl]amino}nonanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2-butyl-1,3-dioxolan-2-yl)-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino}butanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-4-(2-butyl-1,3-dioxan-2-yl)-N-(3-ethylbenzyl)-2-{[(methylamino)carbonyl]amino}butanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5-fluoro-2-{[(methylamino)carbonyl]amino}nonanamide(2R)-N-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-N-(3-ethylbenzyl)-5,5-difluoro-2-{[(methylamino)carbonyl]amino}nonanamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-(3-ethynylbenzyl)-N²-[(methylamino)carbonyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N²-[(methylamino)carbonyl]-N¹-[3-(trifluoromethyl)benzyl]-D-alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-[1-(3-ethyiphenyl)cyclopropyl]-N²-[(methylamino)carbonyl]-D- alaninamideN¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N¹-[1-(3-ethynyiphenyl)cyclopropyl]-N²-[(methylamino)carbonyl]-D- alaninamide,and N¹-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-3-(butylsulfonyl)-N²-[(methylamino)carbonyl]-N¹-{1-[3-(trifluoromethyl)phenyl]cyclopropyl}-D-alaninamide.


12. A method of generating a compound of formula (Y):

comprising exposing a compound according to claim 1 to aqueous media,wherein R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim
 1. 13. Themethod of claim 12 wherein the generation of the compound of formula (Y)occurs in vitro.
 14. The method of claim 12 wherein the generation ofthe compound of formula (Y) occurs in vivo.
 15. The method of claim 12wherein the aqueous media has a pH of about 2 to about
 10. 16. Themethod of claim 3 wherein the aqueous media has a pH of about 3 to about7.
 17. A method for the treatment or prevention of Alzheimer's disease,mild cognitive impairment Down's syndrome, Hereditary CerebralHemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloidangiopathy, other degenerative dementias, dementias of mixed vascularand degenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, diffuse Lewy body type ofAlzheimer's disease comprising administering a therapeutically effectiveamount of a compound or salt according to claim 1, to a patient in needthereof.
 18. A method for the treatment or prevention of Alzheimer'sdisease, mild cognitive impairment Down's syndrome, Hereditary CerebralHemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloidangiopathy, other degenerative dementias, dementias of mixed vascularand degenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, diffuse Lewy body type ofAlzheimer's disease comprising administration of a therapeuticallyeffective amount of a compound or salt according to claim 1, to apatient in need thereof.
 19. The use of a compound or salt according toclaim 1 for the manufacture of a medicament.
 20. The use of a compoundor salt according to claim 1 for the manufacture of a medicament for usein the treatment or prevention of Alzheimer's disease, mild cognitiveimpairment Down's syndrome, Hereditary Cerebral Hemorrhage withAmyloidosis of the Dutch-Type, cerebral amyloid angiopathy, otherdegenerative dementias, dementias of mixed vascular and degenerativeorigin, dementia associated with Parkinson's disease, dementiaassociated with progressive supranuclear palsy, dementia associated withcortical basal degeneration, or diffuse Lewy body type of Alzheimer'sdisease.
 21. A compound according to claim 1 selected frrom the groupconsisting of:


22. A pharmaceutical composition comprising a compound according toclaims 1 in combination with a physiologically acceptable carrier orexcipient.